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Lem2 is essential for cardiac development by maintaining nuclear integrity

ABSTRACT: Lem2 is essential for cardiac development by maintaining nuclear integrity

PROVIDER: PRJNA900158 | ENA |

REPOSITORIES: ENA

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Project description:Lamins and transmembrane proteins within the nuclear envelope regulate nuclear structure and chromatin organization. Nuclear Envelope Transmembrane Protein 39 (Net39) is muscle nuclear envelope protein whose functions in vivo have not been explored. We show that mice lacking Net39 succumb to severe myopathy and juvenile lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression and metabolism. These abnormalities resemble those of Emery-Dreifuss muscular dystrophy (EDMD), caused by mutations in A-type Lamins (LMNA) and other genes, like Emerin (EMD). We observe that Net39 is downregulated in EDMD patients, implicating Net39 in the pathogenesis of this disorder. Our findings highlight the role of Net39 at the nuclear envelope in maintaining muscle chromatin organization, gene expression and function, and its potential contribution to the molecular etiology of EDMD.

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