Overview

Genetic overview

Genetic Background	Generation

a

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

Allele Type	Gene Symbol	Gene Name
Spontaneous	Large1	LARGE xylosyl- and glucuronyltransferase 1

Research Applications

Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Development

The myodystrophy mutation, Large^myd, arose spontaneously at the Jackson Laboratory in the lethal spotting strain (LS/LeJ) in 1963. The first affected male was outcrossed to a C57BL/6J female. Matings of a homozygote by heterozygote were carried out as often as possible or as heterozygous pairs. At F43 in 1977 a Large^myd homozygote was mated to a B6C3Fe-a/a hybrid and the strain was maintained by the cross intercross system to the hybrid. When this strain was at N19, it was cryopreserved by mating heterozygous females to heterozygous males to generate embryos.

Genetics

a

Allele Symbol: a

Allele Name	nonagouti
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)
Strain of Origin	old mutant of the mouse fancy
Chromosome	2
General Note	Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039
Molecular Note	Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for a^t-2Gso and A^w-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.

Large1^myd

Allele Symbol: Large1^myd

Allele Name	myodystrophy
Allele Type	Spontaneous
Allele Synonym(s)	fg; froggy; Large^myd; myd
Gene Symbol and Name	Large1, LARGE xylosyl- and glucuronyltransferase 1
Gene Synonym(s)
Strain of Origin	STOCK Edn3^ls
Chromosome	8
Molecular Note	The mutation underlying the myodystrophy phenotype has been determined to be an intragenic deletion in the glycotransferase gene, Large. The deletion of exons 5-7 cause a frameshift and a premature stop codon before the first two catalytic domains.

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).

muscular dystrophy-dystroglycanopathy

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

facioscapulohumeral muscular dystrophy

Research Areas By Phenotype

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

Neurobiology Research
- Muscular Dystrophy
  - Dystroglycanopathy

Genotype: Large1^myd related

Neurobiology Research
- Muscular Dystrophy
  - Dystroglycanopathy

Mammalian Phenotype Terms by Genotype

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

Genotype: Large1^myd/Large1^myd
MYD/Le-Os +/+ Large/J

growth/size/body region phenotype

abnormal tongue morphology
- musculature of tongue not affected until later
- subepithelial fibrosis in tongues of older mice

postnatal growth retardation
- very severe at weaning
- growth improved after weaning but mice always small

decreased body weight
- organ weights reduced comparably with reduced body weigh

immune system phenotype

myositis
- mononuclear cell infiltration of areas surrounding degenerating fibers

mortality/aging

premature death
- average life span 17.25 weeks, range 5-39 weeks

muscle phenotype

abnormal muscle morphology

abnormal skeletal muscle fiber morphology
- loss of striation
- central migration of nuclei
- variable fiber size
- nuclear "rowing"

dystrophic muscle

myositis
- mononuclear cell infiltration of areas surrounding degenerating fibers

abnormal muscle physiology

calcified muscle
- heart not affected
- elevated calcium levels in skeletal muscles, particularly the diaphragm

muscle degeneration

myopathy
- diffuse and progressive myopathy
- widely distributed focal lesions in skeletal muscles as early as 16 days of age

behavior/neurological phenotype

abnormal gait
- hind limbs never extended and dragged
- hind limbs held close to the body producing a short, shuffling gait

limb grasping
- involves hind limbs
- adduction of hind legs, flexion of the knee, ankles and toes
- severe contraction of hind limbs sometimes by 3-4 months of age

nervous system phenotype

abnormal spinal nerve morphology
- areas completely deficient in myelin
- observed in dorsal roots T13 to S1 and Ventral roots L1 to S1 (except L5)
- L3 and L4 ventral roots most severely affected
- not every root is affected

abnormal myelination
- areas where nerves are completely deficient in myelin

absent Schwann cells
- usually unmyelinated nerves lack Schwann cells but sometimes Schwann cells present but lacking myelin

reproductive system phenotype

reduced fertility
- although not sterile, reproduction is very poor

skeleton phenotype

kyphosis
- thoracic kyphosis by 6-8 weeks of age
- becoming progressively worse with age

abnormal bone structure
- thinning of all bones examined

craniofacial phenotype

abnormal tongue morphology
- musculature of tongue not affected until later
- subepithelial fibrosis in tongues of older mice

digestive/alimentary phenotype

abnormal tongue morphology
- subepithelial fibrosis in tongues of older mice
- musculature of tongue not affected until later

Genotype: Large1^myd/Large1^myd
B6.Cg-Large1/Pjn

cardiovascular system phenotype

abnormal myocardium layer morphology
- lesions observed in the left and right atria and ventricles
- myocardium exhibits mild to moderate areas of cardiomyocyte degeneration with mycytolysis, necrosis and interstitial fibrosis in 5 month old mice

dilated cardiomyopathy
- adult onset

vision/eye phenotype

abnormal eye electrophysiology
- larger negative polarity a-wave in response to intermediate flash intensities in 2 month old mice
- amplitude of b-wave responses is reduced and delayed at all flash intensities in 2 month old mice
- maximum amplitude of a-wave reduced in response to highest flash intensities in 2 month old mice

disorganized retinal outer plexiform layer
- exhibits extracelluelar edema
- layer is thinner than in control littermates
- layer is disorganized with a reduction in synaptic complexes
- mitochondria are swollen with severe disruption of cristae

thin retinal outer nuclear layer
- almost 50% thinner than in controls

abnormal retinal layer morphology

muscle phenotype

abnormal diaphragm morphology
- by 4 months diaphragm exhibits necrosis and fatty infiltration
- exhibits prominent interstial fibrosis with extensive degeneration and regeneration of myofibers at 1.5 months of age

abnormal myocardium layer morphology
- myocardium exhibits mild to moderate areas of cardiomyocyte degeneration with mycytolysis, necrosis and interstitial fibrosis in 5 month old mice
- lesions observed in the left and right atria and ventricles

abnormal soleus morphology
- occasional signs of fiber-type grouping in 6 month old mice

dilated cardiomyopathy
- adult onset

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

Genotype: Large1^myd/Large1^myd
B6C3Fe a/a-Large1/J

behavior/neurological phenotype

abnormal gait
- variable severity at 3 weeks of age; some exhibit gait abnormalities and others could not be identified by this observation

limb grasping
- homozygous mice tightly adduct the hindlimbs and curl toes when suspended by the tail

homeostasis/metabolism phenotype

increased circulating creatine kinase level
- affected animals have an elevated serum CK range compared to controls

abnormal enzyme/coenzyme activity
- laminin-binding activity of alpha-dystroglycan is less than 5% of normal
- mice exhibit hypoglycosylation of almost all alpha-dystroglycan compared to in wild-type mice

immune system phenotype

myositis
- accompanies skeletal muscle fiber necrosis

muscle phenotype

abnormal myocardium layer morphology
- focal interstitial myocardial collagen deposition is seen at 10 months of age, indicating cardiac remodeling that occurs following myocardial damage

calcified muscle
- dystrophic calcification is seen ion areas of skeletal muscle necrosis

skeletal muscle fiber degeneration
- many degenerating and regenerating fibers
- foci of degeneration are typically large, irregularly shaped and involve 20-50 necrotic fibers

skeletal muscle fiber necrosis
- in addition to foci of 20-50 necrotic fibers, individual or smaller groups of necrotic fibers are also seen

abnormal skeletal muscle fiber morphology

centrally nucleated skeletal muscle fibers

dystrophic muscle

abnormal myocardial fiber morphology
- mutants exhibit focal patches of cardiac myocyte membrane damage

increased variability of skeletal muscle fiber size
- both fast and slow muscle fiber types show increased size variation

myositis
- accompanies skeletal muscle fiber necrosis

cardiovascular system phenotype

abnormal myocardium layer morphology
- focal interstitial myocardial collagen deposition is seen at 10 months of age, indicating cardiac remodeling that occurs following myocardial damage

abnormal myocardial fiber morphology
- mutants exhibit focal patches of cardiac myocyte membrane damage

cellular phenotype

skeletal muscle fiber necrosis
- in addition to foci of 20-50 necrotic fibers, individual or smaller groups of necrotic fibers are also seen

growth/size/body region phenotype

decreased body size
- variable severity at 3 weeks of age; some are clearly smaller and others could not be identified by size

hearing/vestibular/ear phenotype

abnormal auditory brainstem response waveform shape
- prolonged I-IV interpeak latencies
- mean wave IV threshold increased
- decreased wave IV amplitude

sensorineural hearing loss

Genotype: Large1^myd/Large1⁺
B6C3Fe a/a-Large1/J

behavior/neurological phenotype

limb grasping
- some aging animals exhibit atypical hindlimb posture and movements when lifted by the tail

References

Additional References

Barresi R; Michele DE; Kanagawa M; Harper HA; Dovico SA; Satz JS; Moore SA; Zhang W; Schachter H; Dumanski JP; Cohn RD; Nishino I; Campbell KP. 2004. LARGE can functionally bypass alpha-dystroglycan glycosylation defects in distinct congenital muscular dystrophies. Nat Med 10(7):696-703PubMed: 15184894 MGI: J:91681
Grewal PK; Hewitt JE. 2002. Mutation of Large, which encodes a putative glycosyltransferase, in an animal model of muscular dystrophy. Biochim Biophys Acta 1573(3):216-24PubMed: 12417403 MGI: J:80112
Lane PW; Beamer TC; Myers DD. 1976. Myodystrophy, a new myopathy on chromosome 8 of the mouse. J Hered 67(3):135-8PubMed: 939913 MGI: J:5670

Additional - a related

Additional - Large1^myd related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Citation
When using the B6C3Fe a/a-Large1^myd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #000226 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
> >	Homozygous for a, ÊHeterozygous or Homozygous or Wild-type for Large<myd>

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

Genetic overview

Research Applications

Base Price

Development

a

Allele Symbol: a

Large1myd

Allele Symbol: Large1myd

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).

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

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

Genotype: Large1myd related

Mammalian Phenotype Terms by Genotype

Genotype: Large1myd/Large1mydMYD/Le-Os +/+ Large/J

growth/size/body region phenotype

immune system phenotype

mortality/aging

muscle phenotype

behavior/neurological phenotype

nervous system phenotype

reproductive system phenotype

skeleton phenotype

craniofacial phenotype

digestive/alimentary phenotype

Genotype: Large1myd/Large1mydB6.Cg-Large1/Pjn

cardiovascular system phenotype

vision/eye phenotype

muscle phenotype

Genotype: Large1myd/Large1mydB6C3Fe a/a-Large1/J

behavior/neurological phenotype

homeostasis/metabolism phenotype

immune system phenotype

muscle phenotype

cardiovascular system phenotype

cellular phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

Genotype: Large1myd/Large1+B6C3Fe a/a-Large1/J

behavior/neurological phenotype

References

Additional References

Additional - a related

Additional - Large1myd related

Genotyping Protocols

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

Large1^myd

Allele Symbol: Large1^myd

Genotype: Large1^myd related

Genotype: Large1^myd/Large1^myd
MYD/Le-Os +/+ Large/J

Genotype: Large1^myd/Large1^myd
B6.Cg-Large1/Pjn

Genotype: Large1^myd/Large1^myd
B6C3Fe a/a-Large1/J

Genotype: Large1^myd/Large1⁺
B6C3Fe a/a-Large1/J

Additional - Large1^myd related