跳转至内容
Merck
  • Net39 protects muscle nuclei from mechanical stress during the pathogenesis of Emery-Dreifuss muscular dystrophy.

Net39 protects muscle nuclei from mechanical stress during the pathogenesis of Emery-Dreifuss muscular dystrophy.

The Journal of clinical investigation (2023-07-03)
Yichi Zhang, Andres Ramirez-Martinez, Kenian Chen, John R McAnally, Chunyu Cai, Mateusz Z Durbacz, Francesco Chemello, Zhaoning Wang, Lin Xu, Rhonda Bassel-Duby, Ning Liu, Eric N Olson
摘要

Mutations in genes encoding nuclear envelope proteins lead to diseases known as nuclear envelopathies, characterized by skeletal muscle and heart abnormalities, such as Emery-Dreifuss muscular dystrophy (EDMD). The tissue-specific role of the nuclear envelope in the etiology of these diseases has not been extensively explored. We previously showed that global deletion of the muscle-specific nuclear envelope protein NET39 in mice leads to neonatal lethality due to skeletal muscle dysfunction. To study the potential role of the Net39 gene in adulthood, we generated a muscle-specific conditional knockout (cKO) of Net39 in mice. cKO mice recapitulated key skeletal muscle features of EDMD, including muscle wasting, impaired muscle contractility, abnormal myonuclear morphology, and DNA damage. The loss of Net39 rendered myoblasts hypersensitive to mechanical stretch, resulting in stretch-induced DNA damage. Net39 was downregulated in a mouse model of congenital myopathy, and restoration of Net39 expression through AAV gene delivery extended life span and ameliorated muscle abnormalities. These findings establish NET39 as a direct contributor to the pathogenesis of EDMD that acts by protecting against mechanical stress and DNA damage.

材料
货号
品牌
产品描述

Sigma-Aldrich
泰莫西芬, ≥99%
Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
抗磷酸组蛋白H2A.X(Ser139)抗体,克隆JBW301, clone JBW301, Upstate®, from mouse
Sigma-Aldrich
黏着斑蛋白单克隆抗体 小鼠抗, clone hVIN-1, ascites fluid
Sigma-Aldrich
细胞色素 C 来源于马心脏, ≥95% (SDS-PAGE)
Sigma-Aldrich
抗层粘连蛋白 兔抗, 0.5 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-GAPDH,克隆6C5, clone 6C5, Chemicon®, from mouse
Sigma-Aldrich
抗-α-微管蛋白抗体,小鼠单克隆, clone DM1A, purified from hybridoma cell culture
Sigma-Aldrich
Anti-SUN2 Antibody, clone 3.1E, clone 3.1E, from mouse
Sigma-Aldrich
Anti-PLPP7 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody