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Journal articles
Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies
Abstract : 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.
https://hal-univ-evry.archives-ouvertes.fr/hal-02321460
Contributor : Olek Maciejak <>
Submitted on : Monday, October 21, 2019 - 11:36:46 AM
Last modification on : Wednesday, May 20, 2020 - 3:10:17 PM
Contributor : Olek Maciejak <>
Submitted on : Monday, October 21, 2019 - 11:36:46 AM
Last modification on : Wednesday, May 20, 2020 - 3:10:17 PM
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