Mice homozygous for the dystrophia-muscularis spontaneous mutations (Lama2^dy and Lama2^dy-2J) are characterized by progressive weakness and paralysis beginning at about 3 1/2 weeks of age. The hindlimbs are affected first, later the axial and forelimb musculature. Death usually occurs before 6 months of age, and mutant mice are usually sterile. Skeletal muscle shows degenerative changes with proliferation of sarcolemmal nuclei, increase in amount of interstitial tissue, and size variation among individual muscle fibers. In the dorsal and ventral roots of the peripheral nerves, both spinal and cranial, Schwann cells fail to separate and ensheathe axons so that groups of closely apposed naked axons, normally seen only in early stages, persist into adulthood. In the rest of the PNS, the basement membrane of Schwann cells is interrupted by gaps, the internodal gap in the nodes of Ranvier is lengthened, and there is delayed onset of myelination with fewer myelinated axons and shorter internode length. Homozygotes are usually sterile.

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 the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Control Suggestions

Heterozygote from the colony
Untyped from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Lama2^dy

Allele Symbol: Lama2^dy

Allele Name	dystrophia muscularis
Allele Type	Spontaneous
Allele Synonym(s)	dy
Gene Symbol and Name	Lama2, laminin, alpha 2
Gene Synonym(s)
Strain of Origin	129P1/Re
Chromosome	10
General Note	This mutation arose spontaneously in the 129/Re inbred strain at The Jackson Laboratory in 1951.
Molecular Note	Analysis of Lama2 expression of dystrophic dy mice revealed a specific deficiency of this mRNA in skeletal muscle, cardiac muscle, and peripheral nerve.

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).

congenital merosin-deficient muscular dystrophy 1A

Research Areas By Phenotype

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

Neurobiology Research
- Muscular Dystrophy
  - Congenital Merosin-Deficient type

Genotype: Lama2^dy related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency Associated with Other Defects
Neurobiology Research
- Myelination Defects
- Muscular Dystrophy
  - Congenital Merosin-Deficient type
Mouse/Human Gene Homologs
- muscular dystrophy, congenital merosin-deficient (CMD)

Mammalian Phenotype Terms by Genotype

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

Genotype: Lama2^dy/Lama2^dy
involves: 129P1/Re * C57BL/6

cellular phenotype

abnormal basal lamina morphology
- the basal lamina of muscles is discontinuous, sparse and enmeshed with collagen fibrils from the collapse of the reticular lamina
- the basal lamina of Schwann cells is sparse
- the basal lamina was absent from non-myelinating Schwann cells

skeletal muscle fiber necrosis

nervous system phenotype

abnormal myelination
- despite adherence of Schwann cells to axons and extension of processes, myelination is not completed
- peripheral nerve roots in the spine exhibit severe hypomyelination

muscle phenotype

abnormal muscle regeneration
- mice exhibit a decreased regenerative capacity with a reduction of total fiber number and a decrease in centrally localized nuclei compared to in wild-type mice

abnormal skeletal muscle fiber morphology
- only a few necrotic fibers are found at 10 days of age but by 15 days of age there are necrotic fibers undergoing phagocytosis and fibers with internal nuclei and by 20 days of age there is an increase in both the number of necrotic and regenerating fibers and a variability in the muscle fiber size
- s and a variability in the muscle fiber size

centrally nucleated skeletal muscle fibers

decreased skeletal muscle fiber number
- the total number of muscle fibers in the soleus is decreased after 15 days of age

increased variability of skeletal muscle fiber size
- evident by 15 days of age
- mutant muscles contain myofibers of different calibers with increased fiber loss and the presence of fibrotic lesions

myopathy

skeletal muscle fiber necrosis

skeletal muscle interstitial fibrosis
- proliferation of interstitial tissue is found skeletal muscle by 20 days of age

Genotype: Lama2^dy/Lama2^dy
involves: 129P1/Re

behavior/neurological phenotype

abnormal sexual interaction
- failure to mate putatively due to physical disability
- gonad morphology is normal

ataxia
- ataxia with occasional unilateral paresis is first observed at 3.5 weeks of age

paresis
- mild paralysis is first observed at 3.5 weeks and progresses to hindlimb dragging by 8 weeks
- paresis is accompanied by spasmodic flexion and flaccid extension in hindlimbs
- unilateral paresis begins at 3.5 weeks progressing to bilateral paresis

mortality/aging

premature death
- most homozygotes die between 1 and 6 months of age

muscle phenotype

abnormal sarcolemma morphology
- unusual proliferation of sarcolemmal nuclei

abnormal skeletal muscle fiber morphology
- affected fibers appear rounded rather than polygonal in transverse section
- in contrast to wild-type, space between fibers is increased and an increase in interstitial tissue is observed
- in some cases, fat cells are found between fibers
- unusual proliferation of nuclei both within and between the fibers

centrally nucleated skeletal muscle fibers
- some fibers, although otherwise normal, contain long chains of centrally, rather than peripherally, located nuclei

dystrophic muscle
- muscular atrophy proceeds from hind quarters to axial and forelimb musculature

increased variability of skeletal muscle fiber size
- individual fibers exhibit size variations

progressive muscle weakness
- eventually there is a complete loss of locomotor function and premature death
- mild paralysis is first observed at 3.5 week and progresses to hindlimb dragging by 8 weeks

skeleton phenotype

kyphosis
- observed at 8 weeks

growth/size/body region phenotype

cachexia
- cachexia as well as thinning and ruffling of fur is observed by 8 weeks

decreased body weight
- by two weeks of age, body weight is less than wildtype
- weight difference continues through out lifespan

Genotype: Lama2^dy/Lama2^dy
129P1/ReJ-Lama2/J

cellular phenotype

abnormal basement membrane morphology
- nodes exhibit unusually long segments bare of basement membrane
- the basement membrane of Schwann cells around myelinated axons is gapped whereas it is absent in amyelinated zones
- the internodal gap in the basement membrane of peripheral nerves at the nodes of Ranvier is lengthened compared to in wild-type mice

growth/size/body region phenotype

decreased body weight

homeostasis/metabolism phenotype

abnormal galactolipid level
- total galactolipid levels in the spinal cord are lower than in wild-type mice

abnormal lipid level
- mice exhibit a decrease in cerebroside sulfatide in the brain compared to wild-type mice
- mice exhibit a reduction in total spinal cord lipid levels and specifically galactolipids and cerebroside sulfatide) compared to wild-type mice

increased cholesterol level
- total cholesterol levels in the spinal cord are higher than in wild-type mice

nervous system phenotype

abnormal axonal transport
- transport of dopamine-beta-hydrolase in nerves is reduced compared to in wild-type mice

abnormal Schwann cell morphology
- after P7, the number of Schwann cell nuclei increases

decreased brain weight

decreased spinal cord weight

demyelination
- fetal axons of less than 0.5 um diameter lack myelin or Schwann cell ensheathment in the peripheral nervous system
- in the dorsal and ventral roots of the spinal and cranial peripheral nerves, Schwann cells fail to separate and ensheathe axons so that groups of closely apposed naked axons, normally seen only in early stages, persist into adulthood
- mice exhibit a 36% decrease in myelinated nerves at the sciatic I level
- myelinated internodal lengths are shorter than in wild-type mice in the peripheral nervous system
- the length of myelinated segments added to an existing population are shorter than in wild-type mice
- the onset of myelination is delayed compared to in wild-type mice

Genotype: Lama2^dy/Lama2^dy
involves: 129P1/ReJ

growth/size/body region phenotype

postnatal growth retardation
- compared to C3^tm1Hrc Lama2^dy homozygotes

skeleton phenotype

scoliosis
- unlike C3^tm1Hrc Lama2^dy homozygotes

hematopoietic system phenotype

increased IgG level
- mice exhibit increased deposition of IgG in muscles compared to in wild-type mice

increased IgM level
- mice exhibit increased deposition of IgM in muscles compared to in wild-type mice and C3^tm1Hrc Lama2^dy homozygotes

immune system phenotype

increased IgG level
- mice exhibit increased deposition of IgG in muscles compared to in wild-type mice

increased IgM level
- mice exhibit increased deposition of IgM in muscles compared to in wild-type mice and C3^tm1Hrc Lama2^dy homozygotes

mortality/aging

premature death
- only 66% of mice survive the 24 week experiment compared to 86% of C3^tm1Hrc Lama2^dy homozygotes

muscle phenotype

abnormal muscle physiology
- mice display hindlimb contractures

dystrophic muscle

muscle weakness
- forelimb strength is decreased compared to in C3^tm1Hrc Lama2^dy homozygotes

skeletal muscle interstitial fibrosis

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

Genotype: Lama2^dy/Lama2^dy
B6.129P1-Lama2/J

behavior/neurological phenotype

abnormal motor capabilities/coordination/movement
- Normal - however, no circling or head twisting is observed
- mice exhibit impaired motor activity

abnormal motor coordination/balance
- mice stumble when walking

hearing/vestibular/ear phenotype

abnormal bony labyrinth
- spaces normally filled with perilymph and endolymph fluids are obliterated with a fibrotic debris

abnormal cochlear hair cell morphology
- hair cells in the organ of Corti not exhibiting their normal vertical height

abnormal inner ear vestibule morphology
- mice exhibit a degeneration of vestibular structures

abnormal organ of Corti morphology
- the structural integrity of the organ of Corti is altered with supporting and hair cells not exhibiting their normal vertical height and a slight compression of the organ, especially at the apical half turn

abnormal organ of Corti supporting cell morphology
- supporting not exhibiting their normal vertical height

absent cochlear hair cells

absent vestibular hair cells

cochlear degeneration

increased or absent threshold for auditory brainstem response
- mice exhibit an increase in brainstem auditory threshold compared to wild-type mice

stria vascularis degeneration

homeostasis/metabolism phenotype

increased circulating prolactin level

muscle phenotype

muscle weakness

nervous system phenotype

abnormal cochlear hair cell morphology
- hair cells in the organ of Corti not exhibiting their normal vertical height

abnormal cochlear nerve morphology
- few if any nerve fibers remain in the ear

absent cochlear hair cells

absent vestibular hair cells

decreased nerve conduction velocity

reproductive system phenotype

decreased testis weight

skeleton phenotype

abnormal bony labyrinth
- spaces normally filled with perilymph and endolymph fluids are obliterated with a fibrotic debris

abnormal cranium morphology
- mice exhibit wider braincases, a slight flexion in the middle and rotated mandibles
- the posterior portion of the skull is slightly expanded while the medial portion is narrowed

increased cranium width
- skull width relative to skull length increase is more pronounced than in Lama2^dy-2J homozygotes

craniofacial phenotype

abnormal bony labyrinth
- spaces normally filled with perilymph and endolymph fluids are obliterated with a fibrotic debris

abnormal cranium morphology
- mice exhibit wider braincases, a slight flexion in the middle and rotated mandibles
- the posterior portion of the skull is slightly expanded while the medial portion is narrowed

increased cranium width
- skull width relative to skull length increase is more pronounced than in Lama2^dy-2J homozygotes

endocrine/exocrine gland phenotype

decreased testis weight

growth/size/body region phenotype

decreased body weight
- drastic

References

Additional References

Meier H; Southard JL. 1970. Muscular dystrophy in the mouse caused by an allele at the dy-locus. Life Sci 9(3):137-44PubMed: 5434356 MGI: J:5151
Sunada Y; Bernier SM; Utani A; Yamada Y; Campbell KP. 1995. Identification of a novel mutant transcript of laminin alpha 2 chain gene responsible for muscular dystrophy and dysmyelination in dy2J mice. Hum Mol Genet 4(6):1055-61PubMed: 7655459 MGI: J:25954
Xu H; Wu XR; Wewer UM; Engvall E. 1994. Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene. Nat Genet 8(3):297-302PubMed: 7874173 MGI: J:21367

Additional - Lama2^dy related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). Homozygotes are usually sterile.
- Additional Breeding and Husbandry Support
Appearance
- black, affected
  Related Genotype: a/a Lama2^dy/Lama2^dy
  
  black, unaffected
  Related Genotype: a/a Lama2^dy/+ or +/?
Citation
When using the dystrophia muscularis mouse strain in a publication, please cite the originating article(s) and include JAX stock #000631 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Progeny testing required but not provided. No genotyping assay is available for these recessive cryo-recovered animals of undefined genotype

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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.

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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.

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Also Known As:dystrophia muscularis

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Additional Information

Lama2dy

Allele Symbol: Lama2dy

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: Lama2dy related

Mammalian Phenotype Terms by Genotype

Genotype: Lama2dy/Lama2dyinvolves: 129P1/Re * C57BL/6

cellular phenotype

nervous system phenotype

muscle phenotype

Genotype: Lama2dy/Lama2dyinvolves: 129P1/Re

behavior/neurological phenotype

mortality/aging

muscle phenotype

skeleton phenotype

growth/size/body region phenotype

Genotype: Lama2dy/Lama2dy129P1/ReJ-Lama2/J

cellular phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

nervous system phenotype

Genotype: Lama2dy/Lama2dyinvolves: 129P1/ReJ

growth/size/body region phenotype

skeleton phenotype

hematopoietic system phenotype

immune system phenotype

mortality/aging

muscle phenotype

Genotype: Lama2dy/Lama2dyB6.129P1-Lama2/J

behavior/neurological phenotype

hearing/vestibular/ear phenotype

homeostasis/metabolism phenotype

muscle phenotype

nervous system phenotype

reproductive system phenotype

skeleton phenotype

craniofacial phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

References

Additional References

Additional - Lama2dy related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Lama2^dy

Allele Symbol: Lama2^dy

Genotype: Lama2^dy related

Genotype: Lama2^dy/Lama2^dy
involves: 129P1/Re * C57BL/6

Genotype: Lama2^dy/Lama2^dy
involves: 129P1/Re

Genotype: Lama2^dy/Lama2^dy
129P1/ReJ-Lama2/J

Genotype: Lama2^dy/Lama2^dy
involves: 129P1/ReJ

Genotype: Lama2^dy/Lama2^dy
B6.129P1-Lama2/J

Additional - Lama2^dy related