MYD/Le Large1^myd/J

Stock number: 018305
Strain synonyms: fg, froggy
Research areas: Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

These Large^myd mice are a model of congenital muscular dystrophy type 1D (MDC1D; also called human α-dystroglycan glycosylation-deficient muscular dystrophy).

Detailed description

The spontaneous autosomal recessive mutation myodystrophy (myd) is a deletion in exons 5-7 of the glycotransferase gene (Large) on chromosome 8; causing a frameshift and premature stop codon before the first two catalytic domains. This Large^myd mutation results in abnormal glycosylation of its substrate α-dystroglycan.
Large^myd mice are a model of Congenital muscular dystrophy type 1D (MDC1D; also called human α-dystroglycan glycosylation-deficient muscular dystrophy). MYD/Le-Large^myd homozygotes exhibit a progressive myopathy, abnormal posture, thoracic kyphosis, calcium deposits in muscle, loss of Schwann cells and myelin, central nervous system defects, and reduced growth. Original characterization of these mice reported that myodystrophic (homozygous) mice were fertile but reproduction was very poor, and the mean lifespan of homozygotes that survived weaning was 17 weeks with a range of 5 to 39 weeks (Lane PW, Beamer TC, and Myers DD. J Hered. 1976. 67:135). As predicted by this, when breeding MYD/Le-Large^myd heterozygotes together at The Jackson Laboratory Repository, MYD/Le-Large^myd homozygous animals were small and died early.
Of note, Large^myd homozygotes on different genetic backgrounds are also described with sensorineural hearing loss (B6C3Fe) and eye defects (C57BL/6). Whether MYD/Le-Large^myd homozygotes manifest these defects is not specifically determined.

Development

The spontaneous autosomal recessive mutation myodystrophy (myd) is a deletion in exons 5-7 of the glycotransferase gene (Large) on chromosome 8; causing a frameshift and premature stop codon before the first two catalytic domains. The history of Stock No. 018305 is described below.

The myodystrophy mutation (Large^myd) was discovered at The Jackson Laboratory in 1963 on the lethal spotting stock LS/LeJ (Stock No. 000262; which had been imported from University College, London in 1961). The first myodystrophic male was outcrossed to a C57BL/6J female. Matings of a homozygous mouse with a heterozygous mouse were carried out as often as possible (or as heterozygous pairs). The Large^myd mutation was found on chromosome 8 in close linkage with the radiation-induced oligosyndactylism mutation (Os; heterozygotes are fertile with fused toes and homozygotes die in utero). As such, a Large^myd/+ male (generation F38) was bred to an ROP inbred female harboring the Os and pintail mutations (Stock No. 000267); this allowed for maintenance/tracking of the Large^myd mutation by Os phenotype). After three sibling matings, oligosyndactylic animals (heterozygous for the Os mutation; Os/+) were crossed seven times to the +/+ members of the strain. At N7, an Os/+ mouse was again crossed to a Large^myd/+ mouse to establish the Os and Large^myd mutations in repulsion. This repulsion strain (Stock No. 000300) was subsequently maintained by breeding oligosyndactylic siblings (Os +/+ Large^myd) together. Stock No. 000300 was cryopreserved in 1981 by mating Os +/+ Large^myd males at N7F22-F27 to non Os (+ +/+ ?) females.

In 2012, heterozygous Large^myd mice without fused toes (wildtype at the Os locus) were obtained and bred together as Stock No. 018305.

Allele

Symbol: Large1^myd
Name: myodystrophy
MGI accession ID: MGI:1856965
Generation method: Spontaneous
Marker symbol: Large1
Marker name: LARGE xylosyl- and glucuronyltransferase 1
Chromosome: 8
Strain of origin: STOCK Edn3^ls
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.