Overview

Mice homozygous for the veils (Large^vls) allele appear runted with muscle wasting. By five months of age, mild to moderate multifocal areas of cardiomyocyte degeneration are observed in the myocardium of homozygotes. Homozygote mice exhibit extensive ocular abnormalities including: retinal dysplasia, a disorganized ganglion cell layer, thinning of the inner nuclear layer, a progressive diminution of photoreceptor cells with aging, as well as, defects in the inner limiting membrane and outer plexiform layer.

Donating Investigator

Patsy Nishina, JAX

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

Large1^vls

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

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Research Applications

Sensorineural Research
Cardiovascular Research
Neurobiology Research

View All Research Applications

Details

Detailed Description

Mice homozygous for the veils (Large^vls) allele appear runted with muscle wasting. By five months of age, mild to moderate multifocal areas of cardiomyocyte degeneration are observed in the myocardium of homozygotes. Homozygote mice exhibit extensive ocular abnormalities including: retinal dysplasia, a disorganized ganglion cell layer, thinning of the inner nuclear layer, a progressive diminution of photoreceptor cells with aging, as well as, defects in the inner limiting membrane and outer plexiform layer. (Lee Y, et al., 2005)

Development

The veils (vls) spontaneous mutation was first identified in the progeny of an F1 cross consisting of the progenitor strains CAST/Ei and a C57BL/6J congenic (N7) carrying the rd7 allele. The donor strain for the congenic was identified as 77-2C2a-special. (Lee Y, et al., 2005) A genome scan of F2 progeny indicated that the spontaneous mutation occurred in a CAST/Ei allele. This congenic has been backcrossed 10 times to C57BL/6J and does not carry the rd7 allele.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Large1^vls

Allele Symbol: Large1^vls

Allele Name	veils
Allele Type	Spontaneous
Allele Synonym(s)	Large^myd-2J
Gene Symbol and Name	Large1, LARGE xylosyl- and glucuronyltransferase 1
Gene Synonym(s)
Strain of Origin	CAST/Ei
Chromosome	8
Molecular Note	Analysis of cDNA from mutant mice revealed a deletion of coding sequences corresponding to exons 3 to 5. This results in a frameshift after codon 35, creating a premature stop codon at position 37 and effectively deleting the coiled coil and catalytic domains from the encoded 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).

muscular dystrophy-dystroglycanopathy

Research Areas By Phenotype

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

Genotype: Large1^vls related

Sensorineural Research
- Eye Defects
Cardiovascular Research
- Heart Abnormalities
  - cardiomyopathy
Neurobiology Research
- Muscular Dystrophy
  - Dystroglycanopathy

Neurobiology Research
- Muscular Dystrophy
  - Dystroglycanopathy

Mammalian Phenotype Terms by Genotype

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

Genotype: Large1^vls/Large1^vls
B6.CAST(Cg)-Large1/Pjn

behavior/neurological phenotype

decreased grip strength
- 50% reduction in grip strength

muscle 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

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

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

dilated cardiomyopathy
- adult onset

vision/eye phenotype

abnormal retinal layer morphology
- layer is thinner than in control littermates
- layer is disorganized with a reduction in synaptic complexes

abnormal retinal vasculature morphology
- retinal vessel tortuosity and increase in number of retinal vessels
- leakage from the vasculature in the perioptic disc region in 25% of mice as determined by fluorescein angiography
- Background Sensitivity - in a segregating C57BL/6 and CAST background retinal vessel tortuosity is highly variable

abnormal vitreous body morphology
- bilateral pigmented or non-pigmented vitreal masses
- bundles of axons and thick walled blood vessels observed in peripheral vitreous

disorganized retinal outer plexiform layer
- layer is disorganized with a reduction in synaptic complexes

abnormal eye electrophysiology
- 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
- larger negative polarity a-wave in response to intermediate flash intensities in 2 month old mice

thin retinal inner nuclear layer
- thinning of layer observed with aging

vitreal fibroplasia

abnormal retinal ganglion layer morphology
- exhibits intracellular edema

thin retinal outer plexiform layer
- layer is thinner than in control littermates

abnormal retinal outer plexiform layer morphology

abnormal retinal inner nuclear layer morphology
- exhibits intracellular edema

abnormal retinal neuronal layer morphology

disorganized retinal ganglion layer
- appears disorganized

vitreous body deposition
- exhibits fibrous tissue in the vitreous body that appears cobweb or veil-like

cardiovascular system phenotype

abnormal retinal vasculature morphology
- leakage from the vasculature in the perioptic disc region in 25% of mice as determined by fluorescein angiography
- retinal vessel tortuosity and increase in number of retinal vessels
- Background Sensitivity - in a segregating C57BL/6 and CAST background retinal vessel tortuosity is highly variable

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

growth/size/body region phenotype

decreased body size

homeostasis/metabolism phenotype

increased circulating creatinine level
- four-fold higher compared to control

References

Additional - Large1^vls related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

Heterozygote x heterozygote matings produce less than the expected 25% homozygous progeny.
- Additional Breeding and Husbandry Support
Appearance
- black
  Related Genotype: a/a

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Large1vls

Allele Symbol: Large1vls

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: Large1vls related

Mammalian Phenotype Terms by Genotype

Genotype: Large1vls/Large1vlsB6.CAST(Cg)-Large1/Pjn

behavior/neurological phenotype

muscle phenotype

vision/eye phenotype

cardiovascular system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

References

Additional - Large1vls related

Genotyping Protocols

Breeding Considerations

Appearance

Terms Of Use

Licensing Information

Large1^vls

Allele Symbol: Large1^vls

Genotype: Large1^vls related

Genotype: Large1^vls/Large1^vls
B6.CAST(Cg)-Large1/Pjn

Additional - Large1^vls related