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Spontaneous cardiac hypertrophy results from the loss of Muscle Ring Finger 1 and 2
Author(s) -
Rodriguez Jessica E,
Li Luge,
Lockyer Pamela,
Patterson Cam,
Willis Monte S
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.466.11
Subject(s) - medicine , myofibril , ring finger , muscle hypertrophy , transcription factor , endocrinology , cardiac muscle , biology , serum response factor , cardiac function curve , chemistry , microbiology and biotechnology , anatomy , gene , heart failure , biochemistry
The muscle ring finger family of proteins (MuRF1‐3) are involved in the regulation of cardiac protein homeostasis. We recently described that MuRF1, like MuRF2, interacts with serum response factor, a transcription factor integral in regulating gene expression involved with cardiac growth. Since hearts from mice lacking either MuRF1 or MuRF2 are normal at baseline, we created MuRF1/MuRF2 double knock‐out mice to directly determine the possible redundancy of MuRF1 and MuRF2 in cardiac structure and function. When we crossed MuRF1/MuRF2 double heterozygous mice, we identified only 3 MuRF1/MuRF2 double null mice out of 231 at weaning, which was significantly less than the 14 (1/16) expected (χ 2 =0.0035). MuRF1/MuRF2 double knock‐out mice died prematurely at an average age of 2 weeks, with extraordinarily large hearts that took up most of the thoracic cavity. These hearts were notably hypertrophic with thickened anterior and posterior ventricular walls. Histologically, the hearts demonstrated increased cardiomyocyte size and extensive transmural fibrosis. These findings suggest overlapping roles of MuRF1 and MuRF2 in the regulation of cardiomyocyte size during development in vivo , consistent with their redundant interactions with proteins such as serum response factor and/or specific myofibrillar proteins they interact with.