Muscles of Dtna (Dtna, dystrobrevin alpha) homozygous mice appear histologically normal during the first two postnatal weeks, but become dystrophic by 1 month of age. Mutant mice exhibit milder pathology than humans with Duchenne dystrophy and never develop the early myofibrosis characteristic of the human disease.
Kevin Campbell, University of IowaRead More +
None of the known alternatively spliced forms of Dtna (Dtna, dystrobrevin alpha) is detectable in non-synaptic portions of skeletal muscles or brains of homozygous mutants, and no compensation by beta-dystrobrevin is detected. Muscles of homozygous mice appear histologically normal during the first two postnatal weeks, but become dystrophic by 1 month of age. Pathological findings include small groups of degenerating myofibers and infiltrating monocytes. Regenerating fibers, characterized by expression of the embryonic myosin heavy chain and central nuclei, are also present. Degenerating muscle cells are usually grouped in clusters of 3-10 fibers. Histologically, the myopathy of homozygous mice resemble that of Dmdmdx (dystrophin, muscular dystrophy; X linked muscular dystrophy) mice, although Dtna homozygous mutants have fewer centrally nucleated fibres. In these mice, as in mdx mice, the diaphragm is the most severely affected skeletal muscle. Overall, however, both Dtna and mdx mutant mice exhibit milder pathology than humans with Duchenne dystrophy and never develop the early myofibrosis characteristic of the human disease.
Exon 3 of the targeted gene was deleted and replaced with a neomycin resistance cassette. A 129/SvJ-derived embryonic stem cell line was used to make the mutation. The strain was backcrossed once to C57BL/6 and was maintained on a mixed 129 and C57BL/6 background by the donating laboratory.
|Allele Name||targeted mutation 1, Joshua R Sanes|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||adbn -; alphaDB-; alphaDbKO|
|Gene Symbol and Name||Dtna, dystrobrevin alpha|
|Gene Synonym(s)||2210407P21Rik; 2210407P21Rik; 87K protein; A0; D18S892E; DRP3; DTN; DTN-A; Dtn; Dtn; Dtna-ps1; LVNC1; RGD1561985; RIKEN cDNA 2210407P21 gene; a-DB-1; adbn; alpha-dystrobrevin; dystrobrevin|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A neomycin resistance cassette replaced a 2.5 kb segment containing exon 3. The deleted sequence corresponds to a region in the protein that is found in the isoforms alpha-DB-1 and alpha DB-2, the only isoforms known to be expressed in muscle. However,immunohistochemical analyses of skeletal muscle and brain did not detect any of the known alternatively spliced isoforms in homozygous mutant mice.|
|Mutations Made By|| |
Joshua Sanes, Harvard University
When maintained in a live colony, heterozygotes or homozygotes may be bred. Homozygotes are reported to be poor breeders and may not start breeding until after 20 weeks of age.
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