P361MIP1 causes cardiomyopathy

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