STIM1 R304W causes muscle degeneration and impaired platelet activation in mice.

ABSTRACT: STIM1 and ORAI1 regulate store-operated Ca²⁺ entry (SOCE) in most cell types, and mutations in these proteins have deleterious and diverse effects. We established a mouse line expressing the STIM1 R304 W gain-of-function mutation causing Stormorken syndrome to explore effects on organ and cell physiology. While STIM1 R304 W was lethal in the homozygous state, surviving mice presented with reduced growth, skeletal muscle degeneration, and reduced exercise endurance. Variable STIM1 expression levels between tissues directly impacted cellular SOCE capacity. In contrast to patients with Stormorken syndrome, STIM1 was downregulated in fibroblasts from Stim1^R304W/R304W mice, which maintained SOCE despite constitutive protein activity. In studies using foetal liver chimeras,

SUBMITTER: Gamage TH 

PROVIDER: S-EPMC6481308 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature