Pathological Mechanisms of Vacuolar Aggregate Myopathy Arising From a Casq1 Mutation

Authors

Amy D Hanna
Chang Seok Lee
Lyle Babcock
Hui Wang
Joseph Recio
Susan L Hamilton

Publication Date

5-1-2021

Journal

The FASEB Journal

DOI

10.1096/fj.202001653RR

PMID

33786938

PMCID

PMC8138327

PubMedCentral® Posted Date

5-1-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Calcium, Calcium-Binding Proteins, Calsequestrin, Endoplasmic Reticulum Stress, Lysosomal Storage Diseases, Male, Mice, Muscle, Skeletal, Muscular Diseases, Mutation, Sarcoplasmic Reticulum, calsequestrin, EC coupling, ER stress, myopathy, sarcoplasmic reticulum

Abstract

Mice with a mutation (D244G, DG) in calsequestrin 1 (CASQ1), analogous to a human mutation in CASQ1 associated with a delayed onset human myopathy (vacuolar aggregate myopathy), display a progressive myopathy characterized by decreased activity, decreased ability of fast twitch muscles to generate force and low body weight after one year of age. The DG mutation causes CASQ1 to partially dissociate from the junctional sarcoplasmic reticulum (SR) and accumulate in the endoplasmic reticulum (ER). Decreased junctional CASQ1 reduces SR Ca

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Associated Data