Cardiac Developmental Defects and Eccentric Right Ventricular Hypertrophy in Cardiomyocyte Focal Adhesion Kinase (FAK) Conditional Knockout Mice

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 May 2

PMID 18448675

Citations 66

Authors

Xu Peng

Xiaoyang Wu

Joseph E Druso

Huijun Wei

Ann Yong-Jin Park

Marc S Kraus

Ana Alcaraz

Ju Chen

Shu Chien

Richard A Cerione

Jun-Lin Guan

Affiliations

Soon will be listed here.

Abstract

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that plays an important role in integrin-mediated signal transduction. To explore the role and mechanisms of FAK in cardiac development, we inactivated FAK in embryonic cardiomyocytes by crossing the floxed FAK mice with myosin light chain-2a (MLC2a) Cre mice, which expressed Cre as early as embryonic day 9.5 in the heart. The majority of conditional FAK knockout mice generated from MLC2a-Cre (CFKO-2a) died in the embryonic stage with thin ventricular wall and ventricular septal defects. A small fraction of CFKO-2a mice survived to adulthood with spontaneous eccentric right ventricle hypertrophy. Transmission electron microscopy analysis displayed swelling in the rough endoplasmic reticulum in CFKO-2a embryonic cardiomyocytes. We found that decreased cell proliferation, but not increased cell apoptosis or differentiation, is the reason for the thin ventricular wall in CFKO-2a mice. Microarray analysis suggests that myocyte enhancer factor 2a (MEF2a) can be regulated by FAK and that inactivation of FAK in the embryonic heart compromised MEF2a expression. Last, we found that Src, but not PI3K, is important in mediating signal transduction for the regulation of MEF2a by FAK. Together, these results identified the role and mechanisms of FAK in embryonic cardiac development.

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