PINCH1 plays an essential role in early murine embryonic development but is dispensable in ventricular cardiomyocytes.
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.
Liang
Xingqun
X
Department of Medicine, University of California at San Diego, School of Medicine, 9500 Gilman Dr., La Jolla, CA 92093-0613, USA.
Zhou
Qiang
Q
Li
Xiaodong
X
Sun
Yunfu
Y
Lu
Min
M
Dalton
Nancy
N
Ross
John
J
Chen
Ju
J
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D047108:Embryonic Development; D017353:Gene Deletion; D015870:Gene Expression; D006352:Heart Ventricles / Q000166:cytology / Q000196:embryology*; D006824:Hybridization, Genetic; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011995:Recombination, Genetic; D016276:Ventricular Function
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C490232:Lims1 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger