Description

Strain Information

Former Names B6.CAST-Largevls/Pjn    (Changed: 14-NOV-05 ) Type Congenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6J Donor Strain CAST/Ei H2 Haplotype b Generation N10F9 (06-NOV-07)

Appearance
black
Related Genotype: a/a

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 Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Large

002491	B6.Cg-Largeenr-Tg(MpbReg)36Pop/J
000226	B6C3Fe a/a-Largemyd/J
000300	MYD/Le-Os +/+ Largemyd/J

View Strains carrying other alleles of Large     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Muscular Dystrophy, Congenital, Type 1d - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Large^vls/Large^vls

        B6.CAST(Cg)-Large^vls/Pjn

• vision/eye phenotype
• abnormal eye electrophysiology (MGI Ref ID J:100214)
  • amplitude of b-wave responses is reduced and delayed at all flash intensities in 2 month old mice
  • larger negative polarity a-wave in response to intermediate flash intensities in 2 month old mice
  • maximum amplitude of a-wave reduced in response to highest flash intensities in 2 month old mice
• abnormal retinal layer morphology (MGI Ref ID J:100214)
  • layer is disorganized with a reduction in synaptic complexes
  • layer is thinner than in control littermates
• abnormal retinal neuronal layer morphology (MGI Ref ID J:100214)
• abnormal retinal ganglion layer morphology (MGI Ref ID J:100214)
  • exhibits intracellular edema
• disorganized retinal ganglion layer (MGI Ref ID J:100214)
  • appears disorganized
• abnormal retinal inner nuclear layer morphology (MGI Ref ID J:100214)
  • exhibits intracellular edema
• thin retinal inner nuclear layer (MGI Ref ID J:100214)
  • thinning of layer observed with aging
• abnormal retinal outer plexiform layer morphology (MGI Ref ID J:100214)
• disorganized retinal outer plexiform layer (MGI Ref ID J:100214)
  • layer is disorganized with a reduction in synaptic complexes
• thin retinal outer plexiform layer (MGI Ref ID J:100214)
  • layer is thinner than in control littermates
• abnormal retinal vasculature (MGI Ref ID J:100214)
  • 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
  • in a segregating C57BL/6 and CAST background retinal vessel tortuosity is highly variable
• abnormal vitreous body (MGI Ref ID J:100214)
  • bilateral pigmented or non-pigmented vitreal masses
  • bundles of axons and thick walled blood vessels observed in peripheral vitreous
• vitreal fibroplasia (MGI Ref ID J:100214)
• vitreous body deposition (MGI Ref ID J:100214)
  • exhibits fibrous tissue in the vitreous body that appears cobweb or veil-like
• muscle phenotype
• abnormal cardiac muscle morphology (MGI Ref ID J:100214)
  • 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 diaphragm morphology (MGI Ref ID J:100214)
  • 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
• abnormal soleus morphology (MGI Ref ID J:100214)
  • occasional signs of fiber-type grouping in 6 month old mice
• dilated cardiomyopathy (MGI Ref ID J:100214)
  • adult onset
• growth/size phenotype
• decreased body size (MGI Ref ID J:100214)
• homeostasis/metabolism phenotype
• increased circulating creatinine level (MGI Ref ID J:100214)
  • four-fold higher compared to control
• behavior/neurological phenotype
• abnormal grip strength (MGI Ref ID J:100214)
  • 50% reduction in grip strength
• cardiovascular system phenotype
• abnormal cardiac muscle morphology (MGI Ref ID J:100214)
  • 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 retinal vasculature (MGI Ref ID J:100214)
  • 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
  • in a segregating C57BL/6 and CAST background retinal vessel tortuosity is highly variable
• dilated cardiomyopathy (MGI Ref ID J:100214)
  • adult onset

View Research Applications

Research Applications

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

Large^vls related

Cardiovascular Research
Heart Abnormalities (cardiomyopathy)

Neurobiology Research
Neuromuscular Defects

Sensorineural Research
Eye Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Largevls
Allele Name		veils
Allele Type		Spontaneous
Strain of Origin		CAST/Ei
Gene Symbol and Name		Large, like-glycosyltransferase
Chromosome		8
Gene Common Name(s)		BPFD#36; KIAA0609; MDC1D; Mbp-1; Mbp1; enervated; enr; fg; froggy; mKIAA0609; myd; myelin basic protein transgene; myodystrophy;
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. [MGI Ref ID J:100214]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Large^vls related

Lee Y; Kameya S; Cox GA; Hsu J; Hicks W; Maddatu TP; Smith RS; Naggert JK; Peachey NS; Nishina PM. 2005. Ocular abnormalities in Large(myd) and Large(vls) mice, spontaneous models for muscle, eye, and brain diseases. Mol Cell Neurosci 30(2):160-72. [PubMed: 16111892]  [MGI Ref ID J:100214]

Litwack ED; Lee Y; Mallott JM. 2006. Absence of the basilar pons in mice lacking a functional Large glycosyltransferase gene suggests a defect in pontine neuron migration. Brain Res 1117(1):12-7. [PubMed: 16956587]  [MGI Ref ID J:114534]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	Heterozygote x heterozygote matings produce less than the expected 25% homozygous progeny.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply	Research Strain. Availability determined by The Jackson Laboratory scientist holding the strain.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

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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.

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