| First Author | Charton K | Year | 2010 |
| Journal | Hum Mol Genet | Volume | 19 |
| Issue | 23 | Pages | 4608-24 |
| PubMed ID | 20855473 | Mgi Jnum | J:165576 |
| Mgi Id | MGI:4837777 | Doi | 10.1093/hmg/ddq388 |
| Citation | Charton K, et al. (2010) Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies. Hum Mol Genet 19(23):4608-24 |
| abstractText | The dominant tibial muscular dystrophy (TMD) and recessive limb-girdle muscular dystrophy 2J are allelic disorders caused by mutations in the C-terminus of titin, a giant sarcomeric protein. Both clinical presentations were initially identified in a large Finnish family and linked to a founder mutation (FINmaj). To further understand the physiopathology of these two diseases, we generated a mouse model carrying the FINmaj mutation. In heterozygous mice, dystrophic myopathology appears late at 9 months of age in few distal muscles. In homozygous (HO) mice, the first signs appear in the Soleus at 1 month of age and extend to most muscles at 6 months of age. Interestingly, the heart is also severely affected in HO mice. The mutation leads to the loss of the very C-terminal end of titin and to a secondary deficiency of calpain 3, a partner of titin. By crossing the FINmaj model with a calpain 3-deficient model, the TMD phenotype was corrected, demonstrating a participation of calpain 3 in the pathogenesis of this disease. |
