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Early postnatal cardiac changes and premature death in transgenic mice overexpressing a mutant form of serum response factor. J Biol Chem 2001 Oct 26;276(43):40033-40

Date

08/22/2001

Pubmed ID

11514558

DOI

10.1074/jbc.M104934200

Scopus ID

2-s2.0-0035955723 (requires institutional sign-in at Scopus site)   69 Citations

Abstract

Serum response factor (SRF) is a key regulator of a number of extracellular signal-regulated genes important for cell growth and differentiation. A form of the SRF gene with a double mutation (dmSRF) was generated. This mutation reduced the binding activity of SRF protein to the serum response element and reduced the capability of SRF to activate the atrial natriuretic factor promoter that contains the serum response element. Cardiac-specific overexpression of dmSRF attenuated the total SRF binding activity and resulted in remarkable morphologic changes in the heart of the transgenic mice. These mice had dilated atrial and ventricular chambers, and their ventricular wall thicknesses were only 1/2 to 1/3 the thickness of that of nontransgenic mice. Also these mice had smaller cardiac myocytes and had less myofibrils in their myocytes relative to nontransgenic mice. Altered gene expression and slight interstitial fibrosis were observed in the myocardium of the transgenic mice. All the transgenic mice died within the first 12 days after birth, because of the early onset of severe, dilated cardiomyopathy. These results indicate that dmSRF overexpression in the heart apparently alters cardiac gene expression and blocks normal postnatal cardiac growth and development.

Author List

Zhang X, Chai J, Azhar G, Sheridan P, Borras AM, Furr MC, Khrapko K, Lawitts J, Misra RP, Wei JY

Author

Ravindra P. Misra PhD Associate Provost, Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Age of Onset
Animals
Cardiomyopathy, Dilated
Female
Heart
Male
Mice
Mice, Transgenic
Muscle Proteins
Mutation
Myocardium
Serum Response Element
Serum Response Factor