An Orai1 gain-of-function tubular aggregate myopathy mouse model phenocopies key features of the human disease.

ABSTRACT: Tubular aggregate myopathy (TAM) is a heritable myopathy primarily characterized by progressive muscle weakness, elevated levels of creatine kinase (CK), hypocalcemia, exercise intolerance, and the presence of tubular aggregates (TAs). Here, we generated a knock-in mouse model based on a human gain-of-function mutation which results in a severe, early-onset form of TAM, by inducing a glycine-to-serine point mutation in the ORAI1 pore (Orai1^G100S/+ or GS mice). By 8 months of age, GS mice exhibited significant muscle weakness, exercise intolerance, elevated CK levels, hypocalcemia, and robust TA presence. Unexpectedly, constitutive Ca²⁺ entry in mutant mice was observed in muscle only during early development and was abolished in adult skeletal muscle, partly due to re

SUBMITTER: Zhao N 

PROVIDER: S-EPMC11612304 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature