1. P361MIP1 causes cardiomyopathy
- Author
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Sawa Kostin, Catherine Mansfield, RL Isaacson, Onjee Choi, G Knoell, Sara J. McSweeney, Hendrik Milting, Byambajav Buyandelger, R Knoell, and Enrique Lara-Pezzi
- Subjects
Calcineurin ,NFATC2 ,Physiology ,Calcineurin Pathway ,Physiology (medical) ,Cardiac myocyte ,Conditional gene knockout ,Myocyte ,Biology ,Cardiology and Cardiovascular Medicine ,CSRP3 ,Molecular biology ,Muscle hypertrophy - Abstract
Purposes: Mutations in sarcomeric proteins are a major cause of hereditary cardiomyopathies. Muscle LIM protein (MLP, CSRP3) is involved in cardiac mechanosensation and important for myocyte-specific survival pathways. Identification of novel MLP interacting proteins (MIP) may provide novel insights into underlying molecular mechanisms of human disease. Methods and Results: Yeast two-hybrid screens identified MIP1 as a novel MLP interacting protein, which is a member of the poxvirus and zinc-finger (POZ or BTB) domain/zinc-finger transcription factor family. The interaction was confirmed by co-immunoprecipitation, cross-linking of recombinant proteins and immunohistochemistry. Cardiac myocyte specific conditional knockout mice (cKO) were generated and underwent transverse aortic constriction (TAC) to unveil potential gene effects. After 4 weeks of TAC left ventricles of cKO mice became dilated (LVIDd mm: 3.74 vs 3.44, LVIDs mm: 2.00 vs 1.65, cKO: n=10, Control: n=8, P
- Published
- 2014