Overview

Also Known As:D2-mdx

The D2.B10 (DBA/2-congenic) Dmd^mdx mouse (also referred to as DBA/2J-mdx or D2-mdx mice) may be a superior Duchenne muscular dystrophy model as it better recapitulates several of the human characteristics of DMD myopathology (lower hind limb muscle weight, fewer myofibers, increased fibrosis and fat accumulation, and muscle weakness) relative to strains with this mutant allele on other genetic backgrounds.

Our preclinical efficacy testing services offer scientific expertise and an array of target-based and phenotype-based outcome measures, both in vivo and at endpoint, for flexible study designs and assay development in mouse models of Muscular Dystrophy. See our full service platform.

Donating Investigator

IMR Colony, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
	?+F17 (2019-06-12 00:00:00)

Dmd^mdx

Allele Type	Gene Symbol	Gene Name
Spontaneous	Dmd	dystrophin, muscular dystrophy

View Genetics

Research Applications

Sensorineural Research
Mouse/Human Gene Homologs
Cell Biology Research
Neurobiology Research

View All Research Applications

Base Price

Starting at:

$139.90 Domestic price for female 5-week

View Price List

Details

Detailed Description

Duchenne muscular dystrophy (DMD) is a progressive muscular disorder caused by an imbalance between muscle degeneration and regeneration resulting in muscle degeneration, necrosis, accumulation of fat and fibrosis, and insufficient regeneration/loss of myofibers. The genetic cause of DMD are mutations of the dystrophin muscular dystrophy gene (DMD) on the X chromosome. The Dmd^mdx mutation in mice has a termination codon in exon 23 that is predicted to result in a truncated protein. Heterozygous females are viable and fertile with no gross phenotypic abnormalities. Homozygous females and hemizygous males are viable and fertile with myopathic features of DMD; although the myopathology is both less severe than the human disease course and variable by mouse strain genetic background.

The muscle pathology observed for C57BL/10ScSn-Dmd^mdx mice (also referred to as C57BL/10-mdx ; Stock No. 001801) includes active fiber necrosis, cellular infiltration, a wide range of fiber sizes, and numerous centrally nucleated regenerating fibers. However, adult C57BL/10-mdx mice fail to exhibit several of the skeletal muscle characteristics of DMD (such as smaller number of myofibers, accumulation of fat and fibrosis, insufficient myofiber regeneration, and loss of muscle weight). In addition, the C57BL/10 inbred strain is shown to possess greater muscle satellite cell self-renewal ability/efficiency than that of the DBA/2 inbred strain which may increase muscle regeneration/attenuate muscular dystrophy phenotype for MD mutations maintained on the C57BL/10 genetic background. As such, The Jackson Laboratory Repository created this DBA/2J-congenic Dmd^mdx mouse model, D2.B10-Dmd^mdx/J (also referred to as DBA/2J-mdx or D2-mdx; Stock No. 013141).

These DBA/2J-mdx mice may be expected to have a phenotype similar to other Dmd^mdx mouse models. That is, when compared to C57BL/10-mdx animals, DBA/2-congenic Dmd^mdx mice exhibit additional DMD characteristics such as lower hind limb muscle weight, fewer myofibers, increased fibrosis and fat accumulation, and remarkable muscle weakness. The DBA/2-congenic Dmd^mdx phenotype is attributed to diminished myofiber regeneration (rather than accelerated myofiber degeneration). Unlike C57BL/10-mdx mice, no increased incidence of spontaneous rhabdomyosarcoma-like tumors are reported for the DBA/2-congenic Dmd^mdx model.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for these DBA/2J-mdx mice (Stock No. 013141). It should be noted that the phenotype could vary from that originally described for C57BL/10-mdx (Stock No. 001801). We will modify the strain description if necessary as published results become available.

Development

The spontaneous mutation "X chromosome-linked muscular dystrophy" (mdx) has as a C-to-T transition resulting in a termination codon at position 2983 (ENSMUST00000114000 chrX:g.83803333 C>T; p.Q995*) within exon 23 of the dystrophin muscular dystrophy gene (Dmd) on the X chromosome [note that Sicinski et al., 1989 originally reported termination codon at position 3185]. C57BL/10ScSn-Dmd^mdx (C57BL/10-mdx) mice are available from The Jackson Laboratory as Stock No. 001801. In 2010, some C57BL/10-mdx mice were backcrossed to DBA/2J inbred mice (Stock No. 000671) for several generations using a marker-assisted, speed congenic approach to generate the D2.B10-congenic strain (also referred to as DBA/2J-mdx) as Stock No. 013141.

Control Suggestions

000671 DBA/2J

Additional Information

Considerations for Choosing Controls

Selected References

Coley WD; Bogdanik L; Vila MC; Yu Q; Van Der Meulen JH; Rayavarapu S; Novak JS; Nearing M; Quinn JL; Saunders A; Dolan C; Andrews W; Lammert C; Austin A; Partridge TA; Cox GA; Lutz C; Nagaraju K. 2016. Effect of genetic background on the dystrophic phenotype in mdx mice. Hum Mol Genet 25(1):130-45PubMed: 26566673 MGI: J:226314
Fukada S; Morikawa D; Yamamoto Y; Yoshida T; Sumie N; Yamaguchi M; Ito T; Miyagoe-Suzuki Y; Takeda S; Tsujikawa K; Yamamoto H. 2010. Genetic background affects properties of satellite cells and mdx phenotypes. Am J Pathol 176(5):2414-24PubMed: 20304955 MGI: J:160773
Ito T; Ogawa R; Uezumi A; Ohtani T; Watanabe Y; Tsujikawa K; Miyagoe-Suzuki Y; Takeda S; Yamamoto H; Fukada S. 2013. Imatinib attenuates severe mouse dystrophy and inhibits proliferation and fibrosis-marker expression in muscle mesenchymal progenitors. Neuromuscul Disord 23(4):349-56PubMed: 23313020 MGI: J:197819

View All References

Genetics

Dmd^mdx

Allele Symbol: Dmd^mdx

Allele Name	X linked muscular dystrophy
Allele Type	Spontaneous
Allele Synonym(s)	mdx; pke; pyruvate kinase expression
Gene Symbol and Name	Dmd, dystrophin, muscular dystrophy
Gene Synonym(s)
Strain of Origin	C57BL/10ScSn
Chromosome	X
Molecular Note	This mutation arose in 1981 in a C57BL/10ScSn colony at University of Leicester. A C-to-T substitution in the CAA codon in exon 23 (ENSMUST00000114000 chrX:g.83803333C>T; c.2983C>T; p.Q995*) results in a termination codon (TAA) in place of a glutamine codon. This allele is predicted to produce a truncated protein.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Duchenne muscular dystrophy

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Dmd^mdx related

Sensorineural Research
- Cataracts
Mouse/Human Gene Homologs
- muscular dystrophy (Duchenne and Becker)
Cell Biology Research
- Signal Transduction
Neurobiology Research
- Muscular Dystrophy
  - Duchenne type

Neurobiology Research
- Neuromuscular defects
- Muscular Dystrophy
  - Duchenne type
Mouse/Human Gene Homologs
- muscular dystrophy (Duchenne and Becker)
Cell Biology Research
- Signal Transduction

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Dmd^mdx/Dmd^mdx
involves: C57BL/10ScSn

cellular phenotype

abnormal skeletal muscle satellite cell proliferation
- satellite cell mitosis is found at 14 days of age and by 28 days increased satellite cells are found in healthy appearing fibers but frequently adjacent to necrotic fibers

skeletal muscle fiber necrosis
- although younger homozygotes do not have fat or fibrous connective tissue in the skeletal muscles, by 270 days of age some fibrous connective tissue is found
- scattered foci of necrotizing fibers surrounded by cellular infiltration can be found in soleus and plantaris muscles as early as 14 days of age, and subsequently in the tibialis anterior, and lastly the extensor digitorum longus with foci of basophilic myotubes being found from 4 weeks of age on
- yotubes being found from 4 weeks of age on

skeletal muscle necrosis
- by 28 days of age necrosis and phagocytosis, with rounded off and swollen mitochondria in the necrotic fibers, is widespread, but is rare at 21 days of age

mammalian phenotype

nervous system phenotype
- Normal - at 8 weeks of age miniature endplate potential frequency, the quantal content of endplate potentials, the amplitude and time course of miniature endplate currents, and the number of acetylcholine receptors at the postsynaptic membrane are all normal

muscle phenotype

abnormal diaphragm morphology
- the diaphragm has a wide variation in myofiber size and architecture, continued necrosis and connective tissue proliferation, and at 16 months of age the diaphragm is pale due to the extensive myofiber loss and replacement fibrosis and the remaining fibe
- at 1.5 years of age the diaphragm is found to have significantly reduced passive stretch capacity although overt respiratory compromise is not found in aging mutants
- at 16 months of age there are twice normal levels of slow myosin in the diaphragm, a decrease in isometric force generation, and a shortened fiber length
- rs are ensheathed in dense collagenous tissue with most having architectural aberrations
- unlike skeletal muscle, the diaphragm undergoes progressive degeneration without regeneration such that, although at 30 days of age foci of myofiber degeneration, necrosis, mineralization, and regeneration are present but not extensive, at 6 months of age the diaphragm has a wide variation in myofiber size and architecture, continued necrosis and connective tissue proliferation, and at 16 months of age the diaphragm is pale due to the extensive myofiber loss and replacement fibrosis and the remaining fibers are ensheathed in dense collagenous tissue with most having architectural aberrations

abnormal intercostal muscle morphology
- the intercostal muscles at 1 to 1.5 years of age have dystrophic changes similar to those of the diaphragm at 6 months of age

abnormal muscle contractility
- scattered hypercontracted fibers are found by electron microscopy at 10 days of age

abnormal muscle electrophysiology
- at 23 degrees hemidiaphragm preparations show lower than normal resting membrane potentials and insertion of a glass microelectrode into a single muscle fiber results in repetitive bursts of muscle action potentials in 30 to 50% of fibers, while at 37 degrees only 7.8% of muscle fibers display this electrical myotonia and the resting membrane potentials are normal
- rees only 7.8% of muscle fibers display this electrical myotonia and the resting membrane potentials are normal

abnormal muscle physiology
- in skeletal muscle fibers myosin magnesium-ATPase activity is higher than normal, myosin B ATPase activity is higher than normal in low free calcium concentrations, and rapid phosphate liberation by magnesium-ATPase is lower than normal

abnormal muscle tone
- at 3 and 32 weeks of age the extensor digitorum longus muscle has decreased twitch and tetanus tension and faster time-to-peak twitch tension compared with controls and the maximum velocity of unloaded shortening is also decreased at 32 weeks of age
- at 4 weeks of age the soleus muscle has decreased twitch and tetanus tension compared with controls, but this is normal by 32 weeks of age

abnormal scalene muscle morphology
- the anterior scalene muscle at 1 to 1.5 years of age show dystrophic changes similar to those of the diaphragm at 6 months of age

abnormal skeletal muscle fiber morphology
- there is almost no fibrous tissue proliferation or adipose tissue replacement
- at 15 days of age necrotic fibers are found, occassionally in clusters, at 20 days of age necrotic fibers are numerous as are groups of regenerating fibers with internally placed nuclei, necrotic fibers are most numerous between 30 and 60 days of age and gradually dissapear although a few scattered necrotic fibers are present at 120 and 180 days of age, and the regenerating fibers increase in size after 30 days of age and almost all of the fibers have internally placed nuclei by 60 to 120 days of age, but there is almost no fibrous tissue proliferation or adipose tissue replacement
- eeks of age in the type 1 fibers of the soleus but not extensor digitorum longus
- electron microscopy shows an accumulation of small pools of non-membrane-bound glycogen from 14 days of age on in both type 1 and type 2 fibers, and membrane-bound vacuoles of variable size and form with finely granular contents are found beginning at 2 weeks of age in the type 1 fibers of the soleus but not extensor digitorum longus
- gradually dissapear although a few scattered necrotic fibers are present at 120 and 180 days of age, and the regenerating fibers increase in size after 30 days of age and almost all of the fibers have internally placed nuclei by 60 to 120 days of age, but
- the extensor digitorum longus, but not the soleus, at 32 weeks of age has a greater proportion of fast-twitch-oxidative-glycolytic fibers and a smaller proportion of fast-twitch-glycolytic fibers than controls

abnormal skeletal muscle morphology
- regenerating fibers, with central nuclei, are most abundant around 35 to 39 days of age when they are approximately 30% of the extensor digitorum longus and 50% of the soleus

abnormal skeletal muscle satellite cell proliferation
- satellite cell mitosis is found at 14 days of age and by 28 days increased satellite cells are found in healthy appearing fibers but frequently adjacent to necrotic fibers

centrally nucleated skeletal muscle fibers
- peripherally nucleated fibers replace the normal fibers in the tibialis anterior, extensor digitorum longus, plantaris, and soleus in a progressive manner, reaching a plateau of 80-90% of fibers at 26 weeks of age

dilated sarcoplasmic reticulum
- from 2 weeks of age in both type 1 and 2 fibers of the extensor digitorum longus and soleus

increased skeletal muscle fiber diameter
- although the number of fibers is normal, the cross-sectional area of the fibers of the tibialis anterior is larger than normal at 3 and 6 months of age
- at 32 weeks of age in the extensor digitorum longus muscle both the slow-twitch-oxidative and fast-twitch-glycolytic fibers have a larger cross-sectional area than those of controls
- at 32 weeks of age in the soleus fast-twitch-oxidative-glycolytic fibers have a larger cross-sectional area than those of controls

increased skeletal muscle mass
- the cross-sectional area and wet weight of the tibialis anterior is greater than normal by 10 weeks of age

skeletal muscle endomysial fibrosis
- found with age in the soleus and plantaris

skeletal muscle fiber necrosis
- although younger homozygotes do not have fat or fibrous connective tissue in the skeletal muscles, by 270 days of age some fibrous connective tissue is found
- scattered foci of necrotizing fibers surrounded by cellular infiltration can be found in soleus and plantaris muscles as early as 14 days of age, and subsequently in the tibialis anterior, and lastly the extensor digitorum longus with foci of basophilic myotubes being found from 4 weeks of age on
- yotubes being found from 4 weeks of age on

skeletal muscle hypertrophy
- detectable up to 12 months of age but not at 15 months of age, at which point muscle fibers appear atrophied and extensively split

skeletal muscle necrosis
- by 28 days of age necrosis and phagocytosis, with rounded off and swollen mitochondria in the necrotic fibers, is widespread, but is rare at 21 days of age

nervous system phenotype

abnormal neuromuscular synapse morphology
- many of which have bouton-like swellings and, rather than the normal confluent pattern at postsynaptic regions, staining of acetylcholine receptors is found in numerous small spots corresponding to the boutons on the motor axon terminals with acetylcholi
- although the nerve terminal innervation of epitronchleoanconeus muscle is normal, the terminal architecture of regenerated muscle fibers, those with central nuclei, are more complex than normal with an increase in the number of fine terminal aborizations, many of which have bouton-like swellings and, rather than the normal confluent pattern at postsynaptic regions, staining of acetylcholine receptors is found in numerous small spots corresponding to the boutons on the motor axon terminals with acetylcholinesterase staining in close association
- electron microscopy shows that neuromuscular junction postsynaptic membranes are variably simplified with a reduction in the number of secondary synaptic folds
- nesterase staining in close association

vision/eye phenotype

anterior subcapsular cataracts
- a slight anterior subcapsular opacity is seen at 4 days of age, which spreads anteriorly such that at 150 days of age there is complete anterior subcapsular opacity in addition to the nuclear opacity
- city

nuclear cataracts
- nuclear opacity of the lens is found at 1 day of age

growth/size/body region phenotype

abnormal scalene muscle morphology
- the anterior scalene muscle at 1 to 1.5 years of age show dystrophic changes similar to those of the diaphragm at 6 months of age

homeostasis/metabolism phenotype

decreased physiological sensitivity to xenobiotic
- injection of the gastrocnemius muscle with chlorpromazine results in a less destruction of calmitine than in controls (20% versus 40%) and has less of an impact on calcium binding to calmitine

Genotype: Dmd^mdx/Dmd^mdx
C57BL/10ScSn-Dmd/J

behavior/neurological phenotype

abnormal grip strength
- performance is similar to that observed in double knockouts

decreased grip strength
- Background Sensitivity - forelimb grip strength is less than Dmd^mdx mice on the DBA/2J background at 28 weeks of age
- reduced forelimb and hindlimb grip strength beginning at 6 weeks as compared to controls

impaired coordination
- performance is similar to that observed in double knockouts

cellular phenotype

skeletal muscle necrosis
- progressive starting at 9 weeks of age

growth/size/body region phenotype

enlarged heart
- enlarged heart as compared to C57BL/10ScSn controls
- enlargement is significant at 52 weeks of age

increased body size
- mice have increased body mass as compared to C57BL/10ScSn controls
- Background Sensitivity - mice have increased body mass as compared to Dmd^mdx mice on the DBA/2J background at 28 weeks

hearing/vestibular/ear phenotype

abnormal auditory brainstem response waveform shape
- prolonged brainstem auditory evoked potential peak and interpeak latencies after noise exposure

increased or absent threshold for auditory brainstem response
- significantly increased hearing threshold after noise exposure

increased susceptibility to noise-induced hearing loss
- daily exposure to noise for 1 month increased hearing threshold and prolonged brainstem auditory evoked potential peak and interpeak latencies

homeostasis/metabolism phenotype

abnormal circulating pyruvate kinase level
- exhibit elevated blood levels of pyruvate kinase

increased circulating creatine kinase level
- elevated levels of serum creatine kinase as compared to C57BL/10ScSn controls at 24 and 28 weeks
- exhibit elevated blood levels of creatine kinase
- Background Sensitivity - levels are higher than Dmd^mdx mice on the DBA/2J background at 24 weeks

increased creatine kinase activity
- Background Sensitivity - activity is higher than Dmd^mdx mice on the DBA/2J background at 24 weeks
- increased creatine kinase activity as compared to C57BL/10ScSn controls at 24 and 28 weeks

immune system phenotype

increased interferon-gamma secretion
- in splenocytes at 2 weeks of age

increased interleukin-12 secretion
- in splenocytes at 2 weeks of age

increased interleukin-2 secretion
- in splenocytes at 2 weeks and 2 years of age

increased interleukin-4 secretion
- in splenocytes at 2 weeks, 4 weeks, and 2 years of age

increased interleukin-6 secretion
- in splenocytes at 2 weeks of age

increased tumor necrosis factor secretion
- in splenocytes at 2 weeks of age

myositis
- hindlimb and forelimb inflammation (as measured by cathepsin activity) is observed at 7 weeks of age
- inflammation and mononuclear cell infiltration is observed in the quadriceps beginning at 7 weeks of age
- Background Sensitivity - unlike Dmd^mdx mice on the DBA/2J background inflammation is not observed in the forelimbs at 52 weeks of age

mammalian phenotype

cardiovascular system phenotype
- Background Sensitivity - mice do not exhibit inflammation in cardiac tissue in contrast to Dmd^mdx mice on the DBA/2J background

muscle phenotype

abnormal muscle morphology

abnormal muscle physiology
- increased intracellular sodium concentration in muscle; increased severity with age

abnormal skeletal muscle fiber morphology
- development of electron-dense bodies in the mitochondria resulting in swelling and degenerating mitochondria, and disruption of the plasmalemma basal lamina
- the normal myofibrillar architecture of bands and lines disappears and myofilaments disintegrate and become misaligned

abnormal skeletal muscle regeneration
- lesions that are observed in quadriceps and diaphragm exhibit muscle degeneration, regeneration and mononuclear infiltrating cells at 7 weeks of age

calcified muscle
- calcium deposits are observed in quadriceps at 52 weeks of age
- Background Sensitivity - however, Dmd^mdx mice on the DBA/2J background develop calcium deposits by 7 weeks of age

cardiomyopathy
- cardiomyopathy is observed at 28 weeks of age
- Background Sensitivity - cardiomyopathy is observed at 7 weeks of age in Dmd^mdx mice on the DBA/2J background

centrally nucleated skeletal muscle fibers
- Background Sensitivity - increase is less than in Dmd^mdx mice on the DBA/2J background than in mice on the C57BL/10ScSn background
- mice exhibit an increased number of centrally nucleated fibers
- Background Sensitivity - myonuclei are predominantly centrally located in contrast to juxtasarcolemmal position in mice on the DBA/2J background

decreased cardiac muscle contractility
- Background Sensitivity - ejection fraction and shortening fraction are higher than in Dmd^mdx mice on the DBA/2J background at 28 weeks of age
- lower ejection fraction and shortening fraction than C57BL/10ScSn controls at 52 weeks of age

dilated sarcoplasmic reticulum

dystrophic muscle
- onset of muscular dystrophy is earlier and more severe in Dmd^mdx mice on the DBA/2J background

impaired skeletal muscle contractility
- decrease in specific force generation in extensor digitorum longus (EDL) as compared to C57BL/10ScSn controls at 28 and 52 weeks of age
- Background Sensitivity - increase in specific and maximum force generation in EDL as compared to Dmd^mdx mice on the DBA/2J background

increased skeletal muscle fiber diameter
- tibialis anterior muscle fibers are increased in diameter (1500 m²) as compared to C57BL/10ScSn mice (375-750 m²)

increased skeletal muscle mass
- increase in muscle mass in gastrocnemius, tibialis anterior and quadriceps as compared to controls
- increased muscle mass in EDL as compared to C57BL/10ScSn control at 28 and 52 weeks of age
- Background Sensitivity - increased muscle mass in EDL as compared to Dmd^mdx mice on the DBA/2J background at 7, 28 and 52 weeks of age

increased variability of skeletal muscle fiber size
- variable muscle fiber size; progressive starting at 3 weeks of age

muscle degeneration
- progressive starting at 3 weeks of age

muscular atrophy
- progressive starting at 3 weeks of age

myopathy
- progressive degenerative myopathy; increased severity with age

myositis
- hindlimb and forelimb inflammation (as measured by cathepsin activity) is observed at 7 weeks of age
- inflammation and mononuclear cell infiltration is observed in the quadriceps beginning at 7 weeks of age
- Background Sensitivity - unlike Dmd^mdx mice on the DBA/2J background inflammation is not observed in the forelimbs at 52 weeks of age

skeletal muscle degeneration
- Background Sensitivity - however, uptake is lower than in Dmd^mdx mice on the DBA/2J background
- increased uptake of Evans blue dye, a measure of muscle damage, as compared to C57BL/10ScSn controls at 8 weeks of age
- lesions that are observed in quadriceps and diaphragm exhibit muscle degeneration, regeneration and mononuclear infiltrating cells at 7 weeks of age

skeletal muscle fibrosis
- exhibit mild muscle fibrosis, however there is no replacement of lost muscle by fat cells

skeletal muscle hypertrophy
- Background Sensitivity - hypertrophy is not observed in Dmd^mdx mice on the DBA/2J background
- muscle hypertrophy observed in gastrocnemius, tibialis anterior and quadriceps

skeletal muscle necrosis
- progressive starting at 9 weeks of age

cardiovascular system phenotype

cardiomyopathy
- cardiomyopathy is observed at 28 weeks of age
- Background Sensitivity - cardiomyopathy is observed at 7 weeks of age in Dmd^mdx mice on the DBA/2J background

decreased cardiac muscle contractility
- Background Sensitivity - ejection fraction and shortening fraction are higher than in Dmd^mdx mice on the DBA/2J background at 28 weeks of age
- lower ejection fraction and shortening fraction than C57BL/10ScSn controls at 52 weeks of age

decreased cardiac output

decreased cardiac stroke volume

enlarged heart
- enlarged heart as compared to C57BL/10ScSn controls
- enlargement is significant at 52 weeks of age

reproductive system phenotype

reduced female fertility
- slight reduction in fertility

Genotype: Dmd^mdx/?
B6.B10ScSn-Dmd

muscle phenotype

abnormal skeletal muscle fiber morphology
- muscles are not stained homogeneously, but streaks of dye representing damaged muscle fibers are observed in the muscle fibers of the diaphragm and gluteus maximus; damage is less severe than in Fgf2/Fgf6/Dmd triple mutants
- when mice are injected with the diazo dye EBD, dye is taken up by damaged muscle fibers to varying degrees, but preferentially into the hindlimb; uptake occurs because of focal breakdown of plasmalemma which is an early event in necrosis

abnormal skeletal muscle morphology
- muscles contain occasional patches of pale tissue which are primarily connective tissue

dystrophic muscle
- mutants show dystrophic changes to the muscle fibers, although less severely than Fgf2/Fgf6/Dmd triple mutants

Genotype: Dmd^mdx/Y
C57BL/10ScSn-Dmd/J

behavior/neurological phenotype

abnormal motor capabilities/coordination/movement

impaired coordination
- mild incoordination noticeable by 12 months of age

tremors
- muscular tremors noticeable by 12 months of age

muscle phenotype

abnormal muscle morphology

abnormal muscle physiology
- increased intracellular sodium concentration in muscle; increased severity with age

abnormal skeletal muscle fiber morphology
- development of electron-dense bodies in the mitochondria resulting in swelling and degenerating mitochondria, and disruption of the plasmalemma basal lamina
- the normal myofibrillar architecture of bands and lines disappears and myofilaments disintegrate and become misaligned

dilated sarcoplasmic reticulum

dystrophic muscle

increased variability of skeletal muscle fiber size
- variable muscle fiber size; progressive starting at 3 weeks of age

muscle degeneration
- progressive starting at 3 weeks of age

muscular atrophy
- progressive starting at 3 weeks of age

myopathy
- progressive degenerative myopathy; increased severity with age

skeletal muscle fibrosis
- exhibit mild muscle fibrosis, however there is no replacement of lost muscle by fat cells

skeletal muscle necrosis
- progressive starting at 9 weeks of age

cellular phenotype

skeletal muscle necrosis
- progressive starting at 9 weeks of age

homeostasis/metabolism phenotype

abnormal circulating pyruvate kinase level
- exhibit elevated blood levels of pyruvate kinase

increased circulating creatine kinase level
- exhibit elevated blood levels of creatine kinase

immune system phenotype

increased interferon-gamma secretion
- in splenocytes at 2 weeks of age

increased interleukin-12 secretion
- in splenocytes at 2 weeks of age

increased interleukin-2 secretion
- in splenocytes at 2 weeks and 2 years of age

increased interleukin-4 secretion
- in splenocytes at 2 weeks, 4 weeks, and 2 years of age

increased interleukin-6 secretion
- in splenocytes at 2 weeks of age

increased tumor necrosis factor secretion
- in splenocytes at 2 weeks of age

Genotype: Dmd^mdx/Y
C57BL/10ScSn-Dmd

adipose tissue phenotype

decreased body fat mass
- decrease in the accumulation of abdominal fat compared to wild-type controls

cellular phenotype

skeletal muscle fiber necrosis

growth/size/body region phenotype

decreased body fat mass
- decrease in the accumulation of abdominal fat compared to wild-type controls

decreased body weight
- between 8 and 20 weeks of age compared to wild-type controls
- Normal - however, body size as determined by measures of tibia length or body length is similar to wild-type controls

mammalian phenotype

behavior/neurological phenotype
- Normal - performance in a rotarod assay is not significantly different from controls in mice at 6 - 20 weeks of age

muscle phenotype
- Normal - limb and diaphragm muscle weights are similar to controls in mice at 1 year of age

behavior/neurological phenotype

abnormal gait
- increased hind paw base width

decreased grip strength
- in fore and hind paws

fatigue
- at 1 year of age, display a decrease in distance traveled after exercise compared to wild-type controls
- at 12 weeks of age, display a decrease in ambulation and increase in rest time after exercise compared to wild-type controls
- at 6 weeks of age, display a decrease in rearings after exercise compared to wild-type controls
- interindividual responses to exercise induced fatigue are highly variable

short stride length
- at 1 year of age

muscle phenotype

abnormal atrium myocardial trabeculae morphology
- atrial trabecular formation is impaired such that trabeculae at E14.5 are long and hook shaped

abnormal intercostal muscle morphology
- 37.5% depletion of intercostal myotubes by E17.5
- intercostal muscle fibers are distributed more sparsely at E17.5 and fetuses have reduced intercostal muscle fiber densities
- misalignment and tangential displacement of myotubes in intercostal muscles at E13.5-E17.5

abnormal muscle contractility
- scattered hypercontracted fibers are found by electron microscopy at 10 days of age

abnormal muscle development
- cultured embryonic muscle stem cells from E11.5 to E17.5 exhibit hyperproliferation and apoptosis
- Pax7+ skeletal muscle stem cell population is reduced and disorganized at E17.5

abnormal myocardial fiber morphology
- cardiac myocyte disorganization

abnormal myotube morphology
- misalignment and tangential displacement of myotubes in intercostal muscles at E13.5-E17.5
- muscles exhibit a small reduction in myotube number at E13.5-E17.5
- myonuclei are more frequently located centrally and slightly further apart in the myotube at E15.5
- myotube alignment is disrupted early in myogenesis
- myotube defects occur earlier in intercostals at E13.5 than proximal limb muscles at E15.5
- myotube width varies more in E13.5-E17.5 muscles than in wild-type muscle
- myotubes are hypotrophic in E13.5-E17.5 muscles
- only central nuclei (not peripheral) are present in E15.5 muscles

abnormal skeletal muscle fiber morphology
- there is almost no fibrous tissue proliferation or adipose tissue replacement
- at 15 days of age necrotic fibers are found, occassionally in clusters, at 20 days of age necrotic fibers are numerous as are groups of regenerating fibers with internally placed nuclei, necrotic fibers are most numerous between 30 and 60 days of age and gradually dissapear although a few scattered necrotic fibers are present at 120 and 180 days of age, and the regenerating fibers increase in size after 30 days of age and almost all of the fibers have internally placed nuclei by 60 to 120 days of age, but there is almost no fibrous tissue proliferation or adipose tissue replacement
- gradually dissapear although a few scattered necrotic fibers are present at 120 and 180 days of age, and the regenerating fibers increase in size after 30 days of age and almost all of the fibers have internally placed nuclei by 60 to 120 days of age, but

centrally nucleated skeletal muscle fibers
- only central nuclei (not peripheral) are present in E15.5 muscles

impaired muscle relaxation
- electromyograms reveal peudomyotonia unlike in wild-type mice

impaired skeletal muscle contractility
- decrease in the tetanic force produced by the diaphragm and extensor digitorum longus muscles compared to wild-type controls

myocardial fiber degeneration
- unlike in wild-type mice, cardiac fiber degeneration with phagocytosis is observed

skeletal muscle fiber degeneration
- mice exhibit skeletal muscle fiber degeneration with phagocytosis unlike in wild-type mice

skeletal muscle fiber necrosis

skeletal muscle fibrosis
- increased collagen deposition in the diaphragm and quadriceps muscles between 12 weeks and 1 year of age

cardiovascular system phenotype

abnormal atrium myocardial trabeculae morphology
- atrial trabecular formation is impaired such that trabeculae at E14.5 are long and hook shaped

abnormal heart atrium morphology
- distention or separation of the myocardial and endocardial cell layers of the atria occurs at E17.5

abnormal myocardial fiber morphology
- cardiac myocyte disorganization

myocardial fiber degeneration
- unlike in wild-type mice, cardiac fiber degeneration with phagocytosis is observed

thick ventricular wall

Genotype: Dmd^mdx/Dmd^mdx
C57BL/10ScSn-Dmd

behavior/neurological phenotype

decreased aerobic running capacity
- Background Sensitivity - mice run shorter distances than wild-type mice, but run farther than Dmd^mdx mice on the DBA/2 backgroun

endocrine/exocrine gland phenotype

abnormal corticotroph morphology
- some corticotrophs have enlarged golgi stacks

increased somatotroph cell size
- dilation of the rough endoplasmic reticulum, enlarged golgi apparatus, and the presence of many dense secretory granules of homogeneous size are characteristics of the hypertrophic somatotrophs of homozygotes

homeostasis/metabolism phenotype

abnormal circulating pyruvate kinase level
- exhibit elevated blood levels of pyruvate kinase

decreased aerobic running capacity
- Background Sensitivity - mice run shorter distances than wild-type mice, but run farther than Dmd^mdx mice on the DBA/2 backgroun

increased circulating creatine kinase level
- exhibit elevated blood levels of creatine kinase
- serum creatine kinase activity is elevated between 12 and 200 days of age
- serum creatine kinase is elevated at 2 months of age

increased growth hormone level
- pituitary growth hormone levels is slightly higher than normal in 8 to 10 month old females

mammalian phenotype

adipose tissue phenotype
- Background Sensitivity - no fat accumulation is observed in contrast to Dmd^mdx mice on the DBA/2 background

homeostasis/metabolism phenotype
- Normal - serum pyruvate kinase activity is normal
- Normal - serum T4 and thyroid stimulating hormone are normal

muscle phenotype
- Background Sensitivity - grip strength scores are similar to wild-type controls in contrast to Dmd^mdx mice on the DBA/2 background
- Background Sensitivity - no muscle fibrosis is observed in contrast to the fibrosis observed Dmd^mdx mice on the DBA/2 background

cardiovascular system phenotype

abnormal atrium myocardial trabeculae morphology
- atrial trabecular formation is impaired such that trabeculae at E14.5 are long and hook shaped

abnormal heart atrium morphology
- distention or separation of the myocardial and endocardial cell layers of the atria occurs at E17.5

abnormal myocardial fiber morphology
- cardiac myocyte disorganization

myocardium necrosis
- 13 of 65 homozygotes display one or two foci of myocardial necrosis between 26 and 303 days of age and the necrotic fibers have sarcoplasmic vacuolation and loss of nuclei

thick ventricular wall

muscle phenotype

abnormal atrium myocardial trabeculae morphology
- atrial trabecular formation is impaired such that trabeculae at E14.5 are long and hook shaped

abnormal intercostal muscle morphology
- 37.5% depletion of intercostal myotubes by E17.5
- intercostal muscle fibers are distributed more sparsely at E17.5 and fetuses have reduced intercostal muscle fiber densities
- misalignment and tangential displacement of myotubes in intercostal muscles at E13.5-E17.5

abnormal muscle development
- cultured embryonic muscle stem cells from E11.5 to E17.5 exhibit hyperproliferation and apoptosis
- Pax7+ skeletal muscle stem cell population is reduced and disorganized at E17.5

abnormal muscle morphology

abnormal myocardial fiber morphology
- cardiac myocyte disorganization

abnormal myotube morphology
- misalignment and tangential displacement of myotubes in intercostal muscles at E13.5-E17.5
- muscles exhibit a small reduction in myotube number at E13.5-E17.5
- myonuclei are more frequently located centrally and slightly further apart in the myotube at E15.5
- myotube alignment is disrupted early in myogenesis
- myotube defects occur earlier in intercostals at E13.5 than proximal limb muscles at E15.5
- myotube width varies more in E13.5-E17.5 muscles than in wild-type muscle
- myotubes are hypotrophic in E13.5-E17.5 muscles
- only central nuclei (not peripheral) are present in E15.5 muscles

abnormal skeletal muscle fiber morphology
- development of electron-dense bodies in the mitochondria resulting in swelling and degenerating mitochondria, and disruption of the plasmalemma basal lamina
- myopathic lesions in skeletal muscle are found by 22 days of age and are characterized by widespread loss of sarcoplasmic structure, vacuolation, and eosinophilia
- myotubes indicative of muscle regeneration are found by 22 days of age and by 31 days of age almost all muscles have numerous myotubes
- the normal myofibrillar architecture of bands and lines disappears and myofilaments disintegrate and become misaligned

centrally nucleated skeletal muscle fibers
- 25% of fibers have non-peripheral nuclei at 26 days of age and 53% at 100 to 303 days of age
- only central nuclei (not peripheral) are present in E15.5 muscles

dilated sarcoplasmic reticulum

dystrophic muscle

increased quadriceps weight
- Background Sensitivity - weight of quadriceps femoris is greater than both wild-type and Dmd^mdx mice on the DBA/2 background

increased skeletal muscle fiber number
- Background Sensitivity - total number of myofibers is greater than total number of myofibers found in Dmd^mdx mice on the DBA/2 background

increased skeletal muscle mass
- Background Sensitivity - in comparison to Dmd^mdx mice on the DBA/2 background

increased skeletal muscle weight
- Background Sensitivity - weights of tibialis anterior and gastrocnemius muscles are greater than both wild-type and Dmd^mdx mice on the DBA/2 background

increased variability of skeletal muscle fiber size
- variable muscle fiber size; progressive starting at 3 weeks of age

muscle degeneration
- progressive starting at 3 weeks of age

muscular atrophy
- progressive starting at 3 weeks of age

myocardium necrosis
- 13 of 65 homozygotes display one or two foci of myocardial necrosis between 26 and 303 days of age and the necrotic fibers have sarcoplasmic vacuolation and loss of nuclei

myopathy
- progressive degenerative myopathy; increased severity with age

skeletal muscle fiber necrosis

skeletal muscle fibrosis
- exhibit mild muscle fibrosis, however there is no replacement of lost muscle by fat cells

skeletal muscle necrosis
- progressive starting at 9 weeks of age

nervous system phenotype

abnormal corticotroph morphology
- some corticotrophs have enlarged golgi stacks

increased somatotroph cell size
- dilation of the rough endoplasmic reticulum, enlarged golgi apparatus, and the presence of many dense secretory granules of homogeneous size are characteristics of the hypertrophic somatotrophs of homozygotes

reproductive system phenotype

reduced female fertility
- slight reduction in fertility

cellular phenotype

myocardium necrosis
- 13 of 65 homozygotes display one or two foci of myocardial necrosis between 26 and 303 days of age and the necrotic fibers have sarcoplasmic vacuolation and loss of nuclei

skeletal muscle fiber necrosis

skeletal muscle necrosis
- progressive starting at 9 weeks of age

Genotype: Dmd^mdx/Y
involves: C57BL/10ScSn

cellular phenotype

skeletal muscle fiber necrosis
- scattered foci of necrotizing fibers surrounded by cellular infiltration can be found in soleus and plantaris muscles as early as 14 days of age, and subsequently in the tibialis anterior, and lastly the extensor digitorum longus with foci of basophilic myotubes being found from 4 weeks of age on
- yotubes being found from 4 weeks of age on

skeletal muscle necrosis
- conspicuous necrosis and regeneration at 3 weeks of age

nervous system phenotype

abnormal neuromuscular synapse morphology
- although the nerve terminal innervation of epitronchleoanoconeus muscle is normal, the terminal architecture of regenerated muscle fibers, those with central nuclei, are more complex than normal with an increase in the number of fine terminal arborizations, many of which have bouton-like swellings and, rather than the normal confluent pattern at postsynaptic regions, staining of acetylcholine receptors is found in numerous small spots corresponding to the boutons on the motor axon terminals with acetylcholinesterase staining in close association
- electron microscopy shows that neuromuscular junction postsynaptic membranes are variably simplified with a reduction in the number of secondary synaptic folds
- linesterase staining in close association
- s, many of which have bouton-like swellings and, rather than the normal confluent pattern at postsynaptic regions, staining of acetylcholine receptors is found in numerous small spots corresponding to the boutons on the motor axon terminals with acetylcho

vision/eye phenotype

anterior subcapsular cataracts
- a slight anterior subcapsular opacity is seen at 4 days of age, which spreads anteriorly such that at 150 days of age there is complete anterior subcapsular opacity in addition to the nuclear opacity
- city

nuclear cataracts
- nuclear opacity of the lens is found at 1 day of age

immune system phenotype

diaphragmitis
- at 3 months of age, the diaphragm shows multiple endomysial foci of mononuclear inflammatory cells

myositis
- at 3 months of age, quadriceps show multiple endomysial foci of mononuclear inflammatory cells
- however, at 6 months, endomysial inflammation is reduced in quadriceps and only scattered inflammatory cells are present

mammalian phenotype

nervous system phenotype
- Normal - at 8 weeks of age miniature endplate potential frequency, the quantal content of endplate potentials, the amplitude and time course of miniature endplate currents, and the number of acetylcholine receptors at the postsynaptic membrane are all normal

vision/eye phenotype
- Normal - hemizygous males between 20 and 24 weeks of age have normal ERG readings even though abnormal b-waves are often found in Duchenne Muscular Dystrophy patients and are found in the mdx-3cv hemizygotes

muscle phenotype

abnormal diaphragm morphology
- the diaphragm has a wide variation in myofiber size and architecture, continued necrosis and connective tissue proliferation, and at 16 months of age the diaphragm is pale due to the extensive myofiber loss and replacement fibrosis and the remaining fibe
- at 1.5 years of age the diaphragm is found to have significantly reduced passive stretch capacity although overt respiratory compromise is not found in aging mutants
- at 16 months of age there are twice normal levels of slow myosin in the diaphragm, a decrease in isometric force generation, and a shortened fiber length
- elevated hydroxyproline in the diaphragm at 24 weeks of age but not at 3 weeks of age
- rs are ensheathed in dense collagenous tissue with most having architectural aberrations
- unlike skeletal muscle, the diaphragm undergoes progressive degeneration without regeneration such that, although at 30 days of age foci of myofiber degeneration, necrosis, mineralization, and regeneration are present but not extensive, at 6 months of age the diaphragm has a wide variation in myofiber size and architecture, continued necrosis and connective tissue proliferation, and at 16 months of age the diaphragm is pale due to the extensive myofiber loss and replacement fibrosis and the remaining fibers are ensheathed in dense collagenous tissue with most having architectural aberrations

abnormal intercostal muscle morphology
- the anterior scalene and intercostal muscles at 1 to 1.5 years of age have dystrophic changes similar to those of the diaphragm at 6 months of age

abnormal muscle electrophysiology
- at 23 degrees hemidiaphragm preparations show lower than normal resting membrane potentials and insertion of a glass microelectrode into a single muscle fiber results in repetitive bursts of muscle action potentials in 30 to 50% of fibers, while at 37 degrees only 7.8% of muscle fibers display this electrical myotonia and the resting membrane potentials are normal
- rees only 7.8% of muscle fibers display this electrical myotonia and the resting membrane potentials are normal

abnormal muscle tone
- at 3 and 32 weeks of age the extensor digitorum longus muscle has decreased twitch and tetanus tension and faster time-to-peak twitch tension compared with controls and the maximum velocity of unloaded shortening is also decreased at 32 weeks of age
- at 4 weeks of age the soleus muscle has decreased twitch and tetanus tension compared with controls, but this is normal by 32 weeks of age

abnormal skeletal muscle fiber morphology
- the extensor digitorum longus, but not the soleus, at 32 weeks of age has a greater proportion of fast-twitch-oxidative-glycolytic fibers and a smaller proportion of fast-twitch-glycolytic fibers than controls

centrally nucleated skeletal muscle fibers
- peripherally nucleated fibers replace the normal fibers in the tibialis anterior, extensor digitorum longus, plantaris, and soleus in a progressive manner, reaching a plateau of 80-90% of fibers at 26 weeks of age

diaphragmitis
- at 3 months of age, the diaphragm shows multiple endomysial foci of mononuclear inflammatory cells

increased skeletal muscle fiber diameter
- although the number of fibers is normal, the cross-sectional area of the fibers of the tibialis anterior is larger than normal at 3 and 6 months of age
- at 32 weeks of age in the extensor digitorum longus muscle both the slow-twitch-oxidative and fast-twitch-glycolytic fibers have a larger cross-sectional area than those of controls
- at 32 weeks of age in the soleus fast-twitch-oxidative-glycolytic fibers have a larger cross-sectional area than those of controls

increased skeletal muscle mass
- the cross-sectional area and wet weight of the tibialis anterior is greater than normal by 10 weeks of age

myositis
- at 3 months of age, quadriceps show multiple endomysial foci of mononuclear inflammatory cells
- however, at 6 months, endomysial inflammation is reduced in quadriceps and only scattered inflammatory cells are present

skeletal muscle endomysial fibrosis
- found with age in the soleus and plantaris
- mice develop progressive endomysial fibrosis with increased collagen III deposition in the diaphragm

skeletal muscle fiber necrosis
- scattered foci of necrotizing fibers surrounded by cellular infiltration can be found in soleus and plantaris muscles as early as 14 days of age, and subsequently in the tibialis anterior, and lastly the extensor digitorum longus with foci of basophilic myotubes being found from 4 weeks of age on
- yotubes being found from 4 weeks of age on

skeletal muscle hypertrophy
- detectable up to 12 months of age but not at 15 months of age, at which point muscle fibers appear atrophied and extensively split

skeletal muscle necrosis
- conspicuous necrosis and regeneration at 3 weeks of age

Genotype: Dmd^mdx/Dmd⁺
involves: C57BL/10ScSn

muscle phenotype

abnormal skeletal muscle fiber morphology
- 10 days of age, and 28% lack dystrophin at 60 days of age
- consistent with X-inactivation, heterozygous females have a mosaic absence of dystrophin, but this diminishes with age such that at 10 days of age 37% of the fibers in a cross section of the quadriceps lack dystrophin staining, at 35 days of age only 18% of fibers lack dystrophin, and by 60 days of age only 4% lack dystrophin, in extraocular muscles the proportions of dystrophin expressing and non-expressing fibers is similar and in cardiac ventricular muscle approximately 30% of fibers lack dystrophin at 10 days of age, and 28% lack dystrophin at 60 days of age
- of fibers lack dystrophin, and by 60 days of age only 4% lack dystrophin, in extraocular muscles the proportions of dystrophin expressing and non-expressing fibers is similar and in cardiac ventricular muscle approximately 30% of fibers lack dystrophin at
- unlike hemizygotes or homozygotes, necrosis of muscle fibers is very rare

Genotype: Dmd^mdx/Y
involves: 129S4/SvJae * C57BL/10ScSn

homeostasis/metabolism phenotype

abnormal circulating pyruvate kinase level
- marked elevation of pyruvate kinase levels is detectable by P21

muscle phenotype

dystrophic muscle
- mice show severe dystrophic changes in the muscle

Genotype: Dmd^mdx/Dmd⁺
involves: 129S4/SvJae * C57BL/10ScSn

homeostasis/metabolism phenotype

abnormal circulating pyruvate kinase level
- moderate elevation of pyruvate kinase levels is detectable by P21

muscle phenotype

dystrophic muscle
- mice show isolated dystrophic changes in the muscle

Genotype: Dmd^mdx/Dmd^mdx
involves: BALB/c * C57BL/10ScSn * C57BL/Ka

behavior/neurological phenotype

impaired exercise endurance
- lower endurance on treadmill than Prkdc^scid Dmd^mdx double mutants
- mice exhibit a shorter time to exhaustion than wild type controls

skeleton phenotype

abnormal vertebral column morphology
- progressive spinal deformity

homeostasis/metabolism phenotype

impaired exercise endurance
- lower endurance on treadmill than Prkdc^scid Dmd^mdx double mutants
- mice exhibit a shorter time to exhaustion than wild type controls

increased transforming growth factor beta level
- costal diaphragm (DIA) has higher quantity of active TGFB1 in comparison to Prkdc^scid Dmd^mdx double mutants although total quantity is similar
- tibialis anterior (TA) and quadricepts (QA) muscles have a higher content of total TGB1 in comparison to Prkdc^scid Dmd^mdx double mutants

muscle phenotype

centrally nucleated skeletal muscle fibers
- 40-45% of muscle fibers exhibit centrally located nuclei
- small, centrally nucleated, regenerating muscle fibers are found in 2 and 12 month old mice

impaired skeletal muscle contractility
- loss of normalized tetanic force is observed in 2 and 12 month old mice

increased skeletal muscle fiber diameter
- area of muscle fibers is 1500-1700 um² and coefficient of variance is 55-65

skeletal muscle fiber degeneration
- degenerating muscle fibers are found in 2 and 12 month old mice

skeletal muscle fibrosis
- high rate of fibrosis is observed in aged 12 month old mice

The following phenotype relates to a compound genotype created using this strain

Genotype: Dmd^mdx/Dmd^mdx
D2.B10-Dmd

adipose tissue phenotype

increased total body fat amount
- Background Sensitivity - increased fat accumulation in comparison to Dmd^mdx mice on the C57BL/10 background

behavior/neurological phenotype

decreased aerobic running capacity
- maximum running speed in both males and females is less than in wild-type mice
- mice run 45% (male) and 56% (female) shorter distances than wild-type
- Background Sensitivity - mice run shorter distances than wild-type and Dmd^mdx mice on the C57BL/10 background

growth/size/body region phenotype

decreased body weight
- decreased body weight as compared to wild-type

homeostasis/metabolism phenotype

decreased aerobic running capacity
- maximum running speed in both males and females is less than in wild-type mice
- mice run 45% (male) and 56% (female) shorter distances than wild-type
- Background Sensitivity - mice run shorter distances than wild-type and Dmd^mdx mice on the C57BL/10 background

muscle phenotype

decreased quadriceps weight
- Background Sensitivity - weight of quadriceps femoris is less than both wild-type and Dmd^mdx mice on the C57BL/10 background

decreased skeletal muscle fiber number
- Background Sensitivity - decreased number of total myofibers in comparison to Dmd^mdx mice on the C57BL/10 background

decreased skeletal muscle mass
- Background Sensitivity - in comparison to Dmd^mdx mice on the C57BL/10 background

decreased skeletal muscle weight
- Background Sensitivity - weights of tibialis anterior and gastrocnemius muscles are less than both wild-type and Dmd^mdx mice on the C57BL/10 background

muscle weakness
- Background Sensitivity - mice exhibit lower grip strength test scores than wild-type mice and Dmd^mdx mice on the C57BL/10 background

skeletal muscle fibrosis
- Background Sensitivity - increased fibrosis volume in quadriceps femoris as compared to Dmd^mdx mice on the C57BL/10 background

Genotype: Dmd^mdx/Dmd^mdx
D2.B10-Dmd/J

behavior/neurological phenotype

decreased grip strength
- Background Sensitivity - forelimb grip strength at 28 weeks is higher than grip strength in Dmd^mdx mice on C57BL/10ScSn background, but still less than controls
- reduced forelimb grip strength at 12 weeks and 24 weeks as compared to controls
- reduced hindlimb grip strength at 24 weeks, as compared to controls, however, gap closes by 52 weeks

growth/size/body region phenotype

decreased body size
- Background Sensitivity - Dmd^mdx mice on the DBA/2J background have reduced body mass as compared to mice on the C57BL/10ScSn background at 28 weeks
- mice have reduced body mass as compared to DBA/2J controls

homeostasis/metabolism phenotype

increased circulating creatine kinase level
- elevated levels of serum creatine kinase as compared to DBA/2J controls at 24 and 28 weeks
- Background Sensitivity - levels are lower at 24 weeks as compared to Dmd^mdx mice on the C57BL/10ScSn background

increased creatine kinase activity
- Background Sensitivity - activity is lower at 24 weeks as compared to Dmd^mdx mice on the C57BL/10ScSn background
- increased creatine kinase activity as compared to DBA/2J controls at 24 and 28 weeks

immune system phenotype

heart inflammation
- Background Sensitivity - inflammation is not observed in in Dmd^mdx mice on the C57BL/10ScSn background
- inflammation within cardiac tissue is observed by 7 weeks of age

myositis
- forelimb and hindlimb inflammation (as measured by cathepsin activity) is observed at 7 weeks of age
- Background Sensitivity - forelimb inflammation at 52 weeks is not observed in mice on on the C57BL/10ScSn background
- inflammation and mononuclear cell infiltration is observed in the quadriceps beginning at 7 weeks of age
- inflammation in the forelimb is still observed at 52 weeks of age

muscle phenotype

abnormal skeletal muscle fiber morphology
- high incidence of primary and complex branching in myofibers from extensor digitorum longus (EDL) in 12 week old male mice

abnormal skeletal muscle regeneration
- lesions that are observed in quadriceps and diaphragm exhibit muscle degeneration, regeneration and mononuclear infiltrating cells at 7 weeks of age

calcified muscle
- calcifications in quadriceps, heart, diaphragm and epicardium of heart at 7 weeks of age
- Background Sensitivity - Dmd^mdx mice on the C57BL/10ScSn background did not exhibit calcifications until 52 weeks of age

cardiac muscle degeneration

cardiomyopathy
- Background Sensitivity - cardiomyopathy is observed at 28 weeks of age in Dmd^mdx mice on the C57BL/10ScSn background
- cardiomyopathy is observed at 7 weeks of age in mice on the DBA/2J background

centrally nucleated skeletal muscle fibers
- Background Sensitivity - increase is less on the DBA/2J background than on the C57BL/10ScSn background
- mice exhibit an increased number of centrally nucleated fibers
- Background Sensitivity - myonuclei are predominantly centrally located on the C57BL/10ScSn background
- myonuclei are predominantly located in juxtasarcolemmal position on the DBA/2J background

decreased cardiac muscle contractility
- Background Sensitivity - ejection fraction and shortening fraction is lower than in Dmd^mdx mice on C57BL/10ScSn background at 28 weeks of age
- lower ejection fraction and shortening fraction than DBA/2J controls at 28 and 52 weeks of age

decreased skeletal muscle fiber diameter
- tibialis anterior muscle fibers are reduced in diameter (375 m²) as compared to DBA/2J mice (375-750 m²)

decreased skeletal muscle fiber size
- decrease in myonuclear domain from EDL at 12 weeks of age
- increase in average number of nuclei per myofiber and decreased F-actin content from EDL at 12 weeks of age
- increased number of small fibers and smaller number of normal sized fibers

decreased skeletal muscle mass
- loss of muscle mass in gastrocnemius, tibialis anterior and quadriceps as compared to controls
- Background Sensitivity - reduced muscle mass in EDL as compared to Dmd^mdx mice on C57BL/10ScSn background at 7, 28 and 52 weeks of age
- reduced muscle mass in extensor digitorum longus (EDL) as compared to DBA/2J at 28 and 52 weeks of age

dystrophic muscle
- Background Sensitivity - onset of muscular dystrophy is later and less severe in Dmd^mdx mice on on the C57BL/10ScSn background

impaired skeletal muscle contractility
- Background Sensitivity - decrease in specific and maximal force generation in EDL at 7 and 28 weeks as compared to Dmd^mdx mice on C57BL/10ScSn background
- decrease in specific and maximal force generation in EDL at 7, 28 and 52 weeks as compared to DBA/2J controls

myositis
- forelimb and hindlimb inflammation (as measured by cathepsin activity) is observed at 7 weeks of age
- Background Sensitivity - forelimb inflammation at 52 weeks is not observed in mice on on the C57BL/10ScSn background
- inflammation and mononuclear cell infiltration is observed in the quadriceps beginning at 7 weeks of age
- inflammation in the forelimb is still observed at 52 weeks of age

skeletal muscle atrophy
- Background Sensitivity - however, muscle hypertrophy is observed in Dmd^mdx mice on the C57BL/10ScSn background
- muscle atrophy is observed in mice on the DBA/2J background

skeletal muscle degeneration
- increased uptake of Evans blue dye, a measure of muscle damage, as compared to DBA/2J controls at 8 weeks of age
- lesions that are observed in quadriceps and diaphragm exhibit muscle degeneration, regeneration and mononuclear infiltrating cells at 7 weeks of age
- Background Sensitivity - uptake is higher than in Dmd^mdx mice on the C57BL/10ScSn background

skeletal muscle fiber atrophy

cardiovascular system phenotype

cardiac muscle degeneration

cardiomyopathy
- Background Sensitivity - cardiomyopathy is observed at 28 weeks of age in Dmd^mdx mice on the C57BL/10ScSn background
- cardiomyopathy is observed at 7 weeks of age in mice on the DBA/2J background

decreased cardiac muscle contractility
- Background Sensitivity - ejection fraction and shortening fraction is lower than in Dmd^mdx mice on C57BL/10ScSn background at 28 weeks of age
- lower ejection fraction and shortening fraction than DBA/2J controls at 28 and 52 weeks of age

decreased cardiac output

decreased cardiac stroke volume
- decreased left ventricular (stroke) volume

dystrophic cardiac calcinosis
- calcifications in quadriceps, heart, diaphragm and epicardium of heart at 7 weeks of age
- Background Sensitivity - Dmd^mdx mice on the C57BL/10ScSn background did not exhibit calcifications until 52 weeks of age

heart inflammation
- Background Sensitivity - inflammation is not observed in in Dmd^mdx mice on the C57BL/10ScSn background
- inflammation within cardiac tissue is observed by 7 weeks of age

References

Coley WD; Bogdanik L; Vila MC; Yu Q; Van Der Meulen JH; Rayavarapu S; Novak JS; Nearing M; Quinn JL; Saunders A; Dolan C; Andrews W; Lammert C; Austin A; Partridge TA; Cox GA; Lutz C; Nagaraju K. 2016. Effect of genetic background on the dystrophic phenotype in mdx mice. Hum Mol Genet 25(1):130-45PubMed: 26566673 MGI: J:226314
Fukada S; Morikawa D; Yamamoto Y; Yoshida T; Sumie N; Yamaguchi M; Ito T; Miyagoe-Suzuki Y; Takeda S; Tsujikawa K; Yamamoto H. 2010. Genetic background affects properties of satellite cells and mdx phenotypes. Am J Pathol 176(5):2414-24PubMed: 20304955 MGI: J:160773
Ito T; Ogawa R; Uezumi A; Ohtani T; Watanabe Y; Tsujikawa K; Miyagoe-Suzuki Y; Takeda S; Yamamoto H; Fukada S. 2013. Imatinib attenuates severe mouse dystrophy and inhibits proliferation and fibrosis-marker expression in muscle mesenchymal progenitors. Neuromuscul Disord 23(4):349-56PubMed: 23313020 MGI: J:197819

Additional References

Quattrocelli M; Capote J; Ohiri JC; Warner JL; Vo AH; Earley JU; Hadhazy M; Demonbreun AR; Spencer MJ; McNally EM. 2017. Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery from injury. PLoS Genet 13(10):e1007070PubMed: 29065150 MGI: J:247827
Verhaart IEC; van de Vijver D; Boertje-van der Meulen JW; Putker K; Adamzek K; Aartsma-Rus A; van Putten M. 2019. A modified diet does not ameliorate muscle pathology in a mouse model for Duchenne muscular dystrophy. PLoS One 14(4):e0215335PubMed: 31017936 MGI: J:274685

Additional - Dmd^mdx related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- End Point Analysis:DmdEnd Point
- Genotyping resources and troubleshooting
Breeding Considerations

The Dmd^mdx mutant allele is on the X chromosome. Mutant mice were bred to DBA/2J inbred mice (Stock No. 000671) for many generations using a marker-assisted, speed congenic approach to establish this congenic strain. When maintaining the live congenic colony, heterozygous or homozygous females may be bred with hemizygous males.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Hemizygote
Citation
When using the D2.B10-Dmd^mdx/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013141 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX12 (Maximum)

Pricing & Availability

Available Now

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	X linked - Females Heterozygous and males wildtype for Dmd<mdx>, 1 pair minimum

Related Products and Services

Frozen Mouse Embryo	D2.B10-Dmd<mdx>/J	$2595.00
Frozen Mouse Embryo	D2.B10-Dmd<mdx>/J	$2595.00
Frozen Mouse Embryo	D2.B10-Dmd<mdx>/J	$3373.50
Frozen Mouse Embryo	D2.B10-Dmd<mdx>/J	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As:D2-mdx

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Dmdmdx

Allele Symbol: Dmdmdx

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Dmdmdx related

Mammalian Phenotype Terms by Genotype

Genotype: Dmdmdx/Dmdmdxinvolves: C57BL/10ScSn

cellular phenotype

mammalian phenotype

muscle phenotype

nervous system phenotype

vision/eye phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

Genotype: Dmdmdx/DmdmdxC57BL/10ScSn-Dmd/J

behavior/neurological phenotype

cellular phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

homeostasis/metabolism phenotype

immune system phenotype

mammalian phenotype

muscle phenotype

cardiovascular system phenotype

reproductive system phenotype

Genotype: Dmdmdx/?B6.B10ScSn-Dmd

muscle phenotype

Genotype: Dmdmdx/YC57BL/10ScSn-Dmd/J

behavior/neurological phenotype

muscle phenotype

cellular phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Dmdmdx/YC57BL/10ScSn-Dmd

adipose tissue phenotype

cellular phenotype

growth/size/body region phenotype

mammalian phenotype

behavior/neurological phenotype

muscle phenotype

cardiovascular system phenotype

Genotype: Dmdmdx/DmdmdxC57BL/10ScSn-Dmd

behavior/neurological phenotype

endocrine/exocrine gland phenotype

homeostasis/metabolism phenotype

mammalian phenotype

cardiovascular system phenotype

muscle phenotype

nervous system phenotype

reproductive system phenotype

cellular phenotype

Genotype: Dmdmdx/Yinvolves: C57BL/10ScSn

cellular phenotype

nervous system phenotype

vision/eye phenotype

immune system phenotype

mammalian phenotype

muscle phenotype

Genotype: Dmdmdx/Dmd+involves: C57BL/10ScSn

muscle phenotype

Genotype: Dmdmdx/Yinvolves: 129S4/SvJae * C57BL/10ScSn

homeostasis/metabolism phenotype

muscle phenotype

Genotype: Dmdmdx/Dmd+involves: 129S4/SvJae * C57BL/10ScSn

homeostasis/metabolism phenotype

muscle phenotype

Genotype: Dmdmdx/Dmdmdxinvolves: BALB/c * C57BL/10ScSn * C57BL/Ka

behavior/neurological phenotype

Dmd^mdx

Allele Symbol: Dmd^mdx

Genotype: Dmd^mdx related

Genotype: Dmd^mdx/Dmd^mdx
involves: C57BL/10ScSn

Genotype: Dmd^mdx/Dmd^mdx
C57BL/10ScSn-Dmd/J

Genotype: Dmd^mdx/?
B6.B10ScSn-Dmd

Genotype: Dmd^mdx/Y
C57BL/10ScSn-Dmd/J

Genotype: Dmd^mdx/Y
C57BL/10ScSn-Dmd

Genotype: Dmd^mdx/Dmd^mdx
C57BL/10ScSn-Dmd

Genotype: Dmd^mdx/Y
involves: C57BL/10ScSn

Genotype: Dmd^mdx/Dmd⁺
involves: C57BL/10ScSn

Genotype: Dmd^mdx/Y
involves: 129S4/SvJae * C57BL/10ScSn

Genotype: Dmd^mdx/Dmd⁺
involves: 129S4/SvJae * C57BL/10ScSn

Genotype: Dmd^mdx/Dmd^mdx
involves: BALB/c * C57BL/10ScSn * C57BL/Ka

Genotype: Dmd^mdx/Dmd^mdx
D2.B10-Dmd

Genotype: Dmd^mdx/Dmd^mdx
D2.B10-Dmd/J

Additional - Dmd^mdx related