B6.129-Dysf^tm1Kcam/J

Stock number: 013149
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

These Dysf (dysferlin) knock-out mutant mice develop a slowly progressive muscular dystrophy. This mutant mouse strain represents a model that may be useful in studies of muscle disease and repair.

Detailed description

Mice homozygous for this targeted mutation are viable, fertile and show a normal growth rate. Mice develop a slowly progressive muscular dystrophy. By the age of 2 months, a few individual necrotic and centrally nucleated fibers can be detected throughout the muscle; the number increases with age. By 8 months, the muscle develops all of the pathological characteristics of muscular dystrophy (e.g. regenerating fibers, split fibers, muscle necrosis with macrophage infiltration and fat replacement). The severity of the pathology varies in different muscles. Muscle fibers are defective in Ca²⁺-dependent sarcolemma resealing/repair. No protein product from the targeted gene is detected in skeletal muscle microsomes. This mutant mouse strain represents a model that may be useful in studies of muscle disease and repair.

Development

A targeting vector containing a neomycin resistance gene was use to replace a 12 kb region containing the last three coding exons of the gene, including the exons coding for the transmembrane domain. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. This strain was backcrossed to C57BL/6 for seven generations by the donating laboratory.

Allele

Symbol: Dysf^tm1Kcam
Name: targeted mutation 1, Kevin P Campbell
MGI accession ID: MGI:2661116
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Dysf
Marker name: dysferlin
Marker synonyms: 2310004N10Rik; FER1L1; LGMD2B; LGMDR2; MMD1
Chromosome: 6
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: 12 kb of sequences at the 3' end of the gene were replaced with a neomycin resistance cassette via homologous recombination. The gene targeting event results in deletion of the last 3 coding exons including the transmembrane domain. Absence of gene expression in homozygous mutant animals was confirmed by Western blot analysis of skeletal muscle microsomes.