title: The muscle ankyrin repeat proteins CARP, Ankrd2, and DARP are not essential for normal cardiac development and function at basal conditions and in response to pressure overload.
abstract: Ankrd1/CARP, Ankrd2/Arpp, and Ankrd23/DARP belong to a family of stress inducible ankyrin repeat proteins expressed in striated muscle (MARPs). The MARPs are homologous in structure and localized in the nucleus where they negatively regulate gene expression as well as in the sarcomeric I-band, where they are thought to be involved in mechanosensing. Together with their strong induction during cardiac disease and the identification of causative Ankrd1 gene mutations in cardiomyopathy patients, this suggests their important roles in cardiac development, function, and disease. To determine the functional role of MARPs in vivo, we studied knockout (KO) mice of each of the three family members. Single KO mice were viable and had no apparent cardiac phenotype. We therefore hypothesized that the three highly homologous MARP proteins may have redundant functions in the heart and studied double and triple MARP KO mice. Unexpectedly, MARP triple KO mice were viable and had normal cardiac function both at basal levels and in response to mechanical pressure overload induced by transverse aortic constriction as assessed by echocardiography and hemodynamic studies. Thus, CARP, Ankrd2, and DARP are not essential for normal cardiac development and function at basal conditions and in response to mechanical pressure overload.
authors.affiliation: Institute of Genetic and Biomedical Research, UOS Milan, National Research Council and Humanitas Clinical and Research Center, Rozzano (Milan), Italy.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Bang
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Yusu
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Dalton
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Peterson
authors.affiliation: Department of Cell and Molecular Biology and Medicine, Karolinska Insititutet, Stockholm, Sweden; Harvard University, Department of Stem Cell and Regenerative Biology, Cambridge, Massachusetts, United States of America.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chien
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D005260:Female; D023061:Gene Order; D018390:Gene Targeting; D056726:Genetic Association Studies; D056426:Genetic Loci; D006321:Heart / Q000196:embryology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: C104844:Ankrd1 protein, mouse; C485877:Ankrd2 protein, mouse; C472288:DARP protein, mouse; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins
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