Mice homozygous for this sarcoglycan beta knock-out develop severe muscular dystrophy and cardiomyopathy.
Kevin Campbell, University of Iowa
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.
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. Chimeric animals were backcrossed to C57BL/6 five times by the donating laboratory.
|Allele Name||targeted mutation 1, Kevin P Campbell|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Sgcb, sarcoglycan, beta (dystrophin-associated glycoprotein)|
|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.|
|Mutations Made By|| |
Kevin Campbell, University of Iowa
When maintaining a live colony, homozygotes are intercrossed. Mice with decreased mobility may benefit from ground grain placed in the bottom of the cage.
When using the Sgcb KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #006833 in your Materials and Methods section.
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