Progressive kidney degeneration in mice lacking tensin.
Tensin is a focal adhesion phosphoprotein that binds to F-actin and contains a functional Src homology 2 domain. To explore the biological functions of tensin, we cloned the mouse tensin gene, determined its program of expression, and used gene targeting to generate mice lacking tensin. Even though tensin is expressed in many different tissues during embryogenesis, tensin null mice developed normally and appeared healthy postnatally for at least several months. Over time, -/- mice became frail because of abnormalities in their kidneys, an organ that expresses high levels of tensin. Mice with overt signs of weakness exhibited signs of renal failure and possessed multiple large cysts in the proximal kidney tubules, but even in tensin null mice with normal blood analysis, cysts were prevalent. Ultrastructurally, noncystic areas showed typical cell-matrix junctions that readily labeled with antibodies against other focal adhesion molecules. In abnormal regions, cell-matrix junctions were disrupted and tubule cells lacked polarity. Taken together, our data imply that, in the kidney, loss of tensin leads to a weakening, rather than a severing, of focal adhesion. All other tissues appeared normal, suggesting that, in most cases, tensin's diverse functions are redundant and may be compensated for by other focal adhesion proteins.
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Department of Molecular Genetics and Cell Biology, The University of Chicago, Illinois 60637, USA.
Yu
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QC
Degenstein
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Chen
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LB
Fuchs
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D000818:Animals; D002448:Cell Adhesion; D016764:Cell Polarity; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005313:Fetal Death / Q000235:genetics; D007365:Intercellular Junctions; D007668:Kidney / Q000002:abnormalities* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000473:pathology*; D007682:Kidney Pelvis / Q000002:abnormalities; D007687:Kidney Tubules, Proximal / Q000473:pathology; D008098:Litter Size; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000172:deficiency* / Q000502:physiology; D009928:Organ Specificity; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000473:pathology*; D011247:Pregnancy; D000070876:Tensins
D008840:Microfilament Proteins; D000070876:Tensins