Cardiomyopathy in transgenic mice with cardiac-specific overexpression of serum response factor. Am J Physiol Heart Circ Physiol 2001 Apr;280(4):H1782-92
Date
03/15/2001Pubmed ID
11247792DOI
10.1152/ajpheart.2001.280.4.H1782Scopus ID
2-s2.0-6644220044 (requires institutional sign-in at Scopus site) 133 CitationsAbstract
Serum response factor (SRF), a member of the MCM1, agamous, deficiens, SRF (MADS) family of transcriptional activators, has been implicated in the transcriptional control of a number of cardiac muscle genes, including cardiac alpha-actin, skeletal alpha-actin, alpha-myosin heavy chain (alpha-MHC), and beta-MHC. To better understand the in vivo role of SRF in regulating genes responsible for maintenance of cardiac function, we sought to test the hypothesis that increased cardiac-specific SRF expression might be associated with altered cardiac morphology and function. We generated transgenic mice with cardiac-specific overexpression of the human SRF gene. The transgenic mice developed cardiomyopathy and exhibited increased heart weight-to-body weight ratio, increased heart weight, and four-chamber dilation. Histological examination revealed cardiomyocyte hypertrophy, collagen deposition, and interstitial fibrosis. SRF overexpression altered the expression of SRF-regulated genes and resulted in cardiac muscle dysfunction. Our results demonstrate that sustained overexpression of SRF, in the absence of other stimuli, is sufficient to induce cardiac change and suggest that SRF is likely to be one of the downstream effectors of the signaling pathways involved in mediating cardiac hypertrophy.
Author List
Zhang X, Azhar G, Chai J, Sheridan P, Nagano K, Brown T, Yang J, Khrapko K, Borras AM, Lawitts J, Misra RP, Wei JYAuthor
Ravindra P. Misra PhD Associate Provost, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ActinsAging
Animals
Atrial Natriuretic Factor
Blotting, Northern
Cardiomyopathies
DNA-Binding Proteins
Dystrophin
Echocardiography
Gene Expression Regulation, Developmental
Genes, fos
Genes, jun
Heart
Humans
Mice
Mice, Transgenic
Myocardium
Myosin Heavy Chains
Nuclear Proteins
Protein Isoforms
Serum Response Factor
Transcription Factors
Ventricular Function, Left