Mice homozygous for the muscular dystrophy with myositis spontaneous mutation (Ttnmdm) can be recognized at 12 days by an unusual stiff and humpbacked posture. Homozygous mutant mice become very stiff and immobile and most are dead by 2 months. Histological sections show severe muscular degeneration with acute chronic myositis. This mutant serves as a model for human tibial muscular dystrophy (TMD) and limb-girdle muscular dystrophy type 2J.
The muscular dystrophy with myositis mutation (mdm) arose spontaneously in 1980 at The Jackson Laboratory in the inbred strain C57BL/6J. It was maintained using ovarian transplant from a homozygous female in to a B6CBAF1 host that was bred to C57BL/6J and the heterozygous offspring were intercrossed. At generation N13 a host female was mated to a C3HeB/FeJ-a/a male making a hybrid B6C3Fe-a/a mdm/+ line. The strain was then maintained by breeding the host females to B6C3Fe-a/a F1 males then intercrossing the offspring, and was backcrossed onto the hybrid line to N14 when, in 1995, embryos were cryopreserved from intercrosses of heterozygous females and heterozygous males.
|Gene Symbol and Name||a, nonagouti|
|Strain of Origin||old mutant of the mouse fancy|
|General Note||Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039|
|Molecular Note||Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for at-2Gso and Aw-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.|
|Allele Name||muscular dystrophy with myositis|
|Gene Symbol and Name||Ttn, titin|
|Strain of Origin||C57BL/6J|
|General Note||Genbank ID for this allele: AF426842, AF426843|
|Molecular Note||A complex rearrangement involving the deletion of 3 bp of exon C and all of exons D and E (a total of 779 bp) and the in-frame insertion of a 5'-truncated LINE-1 retrotransposon (~2.4 kb). The deletion is predicted to elminate the final 21 residues of the CAPN3 binding site. Low levels of expression of the partial LINE sequence were detected by RT-PCR analysis.|
When maintaining a live colony, heterozygous mice may be bred to wildtype siblings, or to B6C3FeF1/J a/a mice (Stock No. 001022). Homozygous mutant mice become very stiff and immobile and most are dead by 2 months.
When using the muscular dystrophy with myositis mouse strain in a publication, please cite the originating article(s) and include JAX stock #001512 in your Materials and Methods section.