Skeletal muscle-specific Sidt2 knockout in mice induced muscular dystrophy-like phenotype

Metabolism: Clinical and Experimental
Huan LiuHuiwen Zhang

Abstract

Sidt2 is an integral lysosomal membrane protein. Previously, we generated a Sidt2 global knockout mouse and found impaired insulin secretion, along with skeletal muscle pathology. A mouse model with a muscle-specific knockout of the Sidt2 gene (Sidt2f/fCre) had been generated, to which extensive morphologic study as well as functional study was applied to investigate the direct role of Sidt2 on skeletal muscle tissue in vivo. Secondly, the autophagy-lysosomal pathway was examined by Western blot and immunostaining. Additionally, RNA expression changes in Sidt2f/fCre mice were analyzed by genechip. Sidt2 deficiency in skeletal muscle results in pathognomonic hallmarks of muscular dystrophy, including muscle mass decrease, muscle weakness, fibrosis, central nucleation, fiber regeneration, mildly elevated serum creatine kinase, and dramatically elevated sarcolipin mRNA. Along with accumulation of autophagolysomes, LC3-II, adaptor protein p62, ubiquitinated aggregates, and Lamp2-positive vacuoles were increased significantly in Sidt2f/fCre skeletal muscle fibers. However, only lysosomal-related genes were upregulated, while the genes upstream of the autophagy pathway were unchanged. Simultaneously, the proteasome chymotryptic activ...Continue Reading

Citations

Mar 15, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lizhuo WangJialin Gao
Mar 19, 2021·Frontiers in Physiology·Naresh C BalMuthu Periasamy

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