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  • Myopalladin knockout mice develop cardiac dilation and show a maladaptive response to mechanical pressure overload.

Myopalladin knockout mice develop cardiac dilation and show a maladaptive response to mechanical pressure overload.

eLife (2021-09-25)
Maria Carmela Filomena, Daniel L Yamamoto, Pierluigi Carullo, Roman Medvedev, Andrea Ghisleni, Nicoletta Piroddi, Beatrice Scellini, Roberta Crispino, Francesca D'Autilia, Jianlin Zhang, Arianna Felicetta, Simona Nemska, Simone Serio, Chiara Tesi, Daniele Catalucci, Wolfgang A Linke, Roman Polishchuk, Corrado Poggesi, Mathias Gautel, Marie-Louise Bang
ABSTRACT

Myopalladin (MYPN) is a striated muscle-specific immunoglobulin domain-containing protein located in the sarcomeric Z-line and I-band. MYPN gene mutations are causative for dilated (DCM), hypertrophic, and restrictive cardiomyopathy. In a yeast two-hybrid screening, MYPN was found to bind to titin in the Z-line, which was confirmed by microscale thermophoresis. Cardiac analyses of MYPN knockout (MKO) mice showed the development of mild cardiac dilation and systolic dysfunction, associated with decreased myofibrillar isometric tension generation and increased resting tension at longer sarcomere lengths. MKO mice exhibited a normal hypertrophic response to transaortic constriction (TAC), but rapidly developed severe cardiac dilation and systolic dysfunction, associated with fibrosis, increased fetal gene expression, higher intercalated disc fold amplitude, decreased calsequestrin-2 protein levels, and increased desmoplakin and SORBS2 protein levels. Cardiomyocyte analyses showed delayed Ca2+ release and reuptake in unstressed MKO mice as well as reduced Ca2+ spark amplitude post-TAC, suggesting that altered Ca2+ handling may contribute to the development of DCM in MKO mice.

MATERIALS
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Product Description

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