The nSMase2/Smpd3 gene modulates the severity of muscular dystrophy and the emotional stress response in mdx mice.

BMC Medicine
Yasunari MatsuzakaKazuo Hashido

Abstract

Duchenne muscular dystrophy (DMD) is a progressive, degenerative muscular disorder and cognitive dysfunction caused by mutations in the dystrophin gene. It is characterized by excess inflammatory responses in the muscle and repeated degeneration and regeneration cycles. Neutral sphingomyelinase 2/sphingomyelin phosphodiesterase 3 (nSMase2/Smpd3) hydrolyzes sphingomyelin in lipid rafts. This protein thus modulates inflammatory responses, cell survival or apoptosis pathways, and the secretion of extracellular vesicles in a Ca2+-dependent manner. However, its roles in dystrophic pathology have not yet been clarified. To investigate the effects of the loss of nSMase2/Smpd3 on dystrophic muscles and its role in the abnormal behavior observed in DMD patients, we generated mdx mice lacking the nSMase2/Smpd3 gene (mdx:Smpd3 double knockout [DKO] mice). Young mdx:Smpd3 DKO mice exhibited reduced muscular degeneration and decreased inflammation responses, but later on they showed exacerbated muscular necrosis. In addition, the abnormal stress response displayed by mdx mice was improved in the mdx:Smpd3 DKO mice, with the recovery of brain-derived neurotrophic factor (Bdnf) expression in the hippocampus. nSMase2/Smpd3-modulated lipid raft...Continue Reading

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Citations

Nov 16, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Angus LindsayAaron P Russell

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Methods Mentioned

BETA
PCR
electrophoresis
Assay
transgenic
dissection
profiler
chips
protein array
antisense oligonucleotide
SMase

Software Mentioned

Power / Size Calculator
SDS
BLAST
CRISPR Design Tool
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NIH Image

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