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5-integrin results in perinatal lethality
Mayo Clinic Scottsdale, Scottsdale, Arizona 85259
Communication between the
extracellular matrix and the intracellular signal transduction and
cytoskeletal system is mediated by integrin receptors.
5
1-Integrin and its cognate ligand
fibronectin are essential in development of mesodermal structures,
myocyte differentiation, and normal cardiac development. To begin to
explore the potential roles of
51-integrin specifically in
cardiomyocytes, we used a transgenic expression strategy. We
overexpressed two forms of the human 5-integrin in
cardiomyocytes: the full-length wild-type
5-integrin and a putative gain-of-function mutation created by truncating the cytoplasmic domain, designated
5-1-integrin. Overexpression of the wild-type
5-integrin has no detectable adverse effects in the
mouse, whereas expression of 5-1-integrin caused
electrocardiographic abnormalities, fibrotic changes in the ventricle,
and perinatal lethality. Thus physiological regulation of integrin
function appears essential for maintenance of normal cardiomyocyte
structure and function. This strengthens the role of inside-out
signaling in regulation of integrins in vivo and suggests that
integrins and associated signaling molecules are important in
cardiomyocyte function.
inside-out signaling; electrocardiogram abnormalities; cardiomyopathy; fibrosis
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