129-Sgcb^tm1Kcam/J

Stock number: 006831
Product name: Sgcb KO
Strain synonyms: Q201 x129S3 Sv1MJ
Research areas: Cardiovascular Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

Mice homozygous for this sarcoglycan beta knock-out develop severe muscular dystrophy and cardiomyopathy.

Detailed description

Homozyous mice are viable and fertile. They develop severe muscular dystrophy and cardiomyopathy with focal areas of necrosis. Severe dystrophic changes including necrosis, dystrophic calcification, fatty infiltration, central nucleation, fibrosis, atrophy and hypertrophy are detected in diaphragm and calf/thigh muscle. Some of these changes occur in 4-week-old animals and accumulate with age. At 20 weeks of age, several regions of focal myocardial necrosis have been observed; small areas of necrotic myocardiocytes may be observed as early as 9 weeks of age. At 30 weeks of age, large areas of fibrosis are detected. Sarcoglycan-sarcospan and dystroglycan complexes are disrupted in skeletal, cardiac, and smooth muscle membranes. Loss of the sarcoglycan-sarcospan complex in vascular smooth muscle results in vascular irregularities in heart, diaphragm, and kidneys. Vascular constrictions in skeletal muscle, cardiac muscle and kidneys is observed. Epsilon-sarcoglycan (SGCE) is also reduced in membrane preparations of striated and smooth muscle. The muscular dystrophy phenotype is reportedly more severe on the 129 background than the C57BL/6 background. Northern blot analysis of skeletal muscle with an exon 6 probe reveals no transcript in the skeletal muscle of homozygous mice. This mutant mouse strain represents a model that may be useful in studies of muscular dystrophy, cardiomyopathy, and smooth muscle dysfunction.

Development

A targeting vector containing a neomycin resistance gene was used to replace exons 3-6 of the gene. 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 C57BL/6 blastocysts.

Allele

Symbol: Sgcb^tm1Kcam
Name: targeted mutation 1, Kevin P Campbell
MGI accession ID: MGI:2153048
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Sgcb
Marker name: sarcoglycan, beta (dystrophin-associated glycoprotein)
Marker synonyms: A3b; beta-SG; LGMD2E; LGMDR4; SGC
Chromosome: 5
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A loxP flanked neomycin cassette replaced a genomic fragment that contained exons 3-6. These exons encode part of the transmembrane domain and the extracellular portion of the protein. Northern blot analysis revealed that no transcript was detectable in skeletal muscle of homozygous mice and Western blot and immunohistochemical analysis demonstrated that the protein was absent in the sarcolemma of skeletal muscle derived from homozygous mice.