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Molecular and Cellular Biology, April 2005, p. 3056-3062, Vol. 25, No. 8
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.8.3056-3062.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

PINCH1 Plays an Essential Role in Early Murine Embryonic Development but Is Dispensable in Ventricular Cardiomyocytes

Xingqun Liang, Qiang Zhou, Xiaodong Li, Yunfu Sun, Min Lu, Nancy Dalton, John Ross Jr., and Ju Chen*

Institute of Molecular Medicine, Department of Medicine, University of California, San Diego, La Jolla, California

Received 13 October 2004/ Returned for modification 21 November 2004/ Accepted 13 January 2005

PINCH1, an adaptor protein composed of five LIM domains, mediates protein-protein interactions and functions as a component of the integrin-integrin-linked kinase (ILK) complex. The integrin-ILK signaling complex plays a pivotal role in cell motility, proliferation, and survival during embryonic development of many animal species. To elucidate the physiological function of PINCH1 in mouse embryonic development, we have deleted the mouse PINCH1 gene by homologous recombination. Mice heterozygous for PINCH1 are viable and indistinguishable from wild-type littermates. However, no viable homozygous offspring were observed from PINCH1+/ intercrosses. Histological analysis of homozygous mutant embryos revealed that they had a disorganized egg cylinder by E5.5, which degenerated by E6.5. Furthermore, E5.5 PINCH1/ embryos exhibited decreased cell proliferation and excessive cell death. We have also generated and analyzed mice in which PINCH1 has been specifically deleted in ventricular cardiomyocytes. These mice exhibit no basal phenotype, with respect to mouse survival, cardiac histology, or cardiac function as measured by echocardiography. Altogether, these data indicate that PINCH1 plays an essential role in early murine embryonic development but is dispensable in ventricular cardiomyocytes.


* Corresponding author. Mailing address: Department of Medicine, University of California at San Diego, School of Medicine, 9500 Gilman Dr., La Jolla, CA 92093-0613. Phone: (858) 822-2452. Fax: (858) 534-2069. E-mail: juchen{at}ucsd.edu.


Molecular and Cellular Biology, April 2005, p. 3056-3062, Vol. 25, No. 8
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.8.3056-3062.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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