PROGRESSIVE KIDNEY DEGENERATION IN MICE LACKING TENSIN

Tensin is a focal adhesion phosphoprotein that binds to F-actin and co ntains a functional Src homology 2 domain. To explore the biological f unctions of tensin, we cloned the mouse tensin gene, determined its pr ogram of expression, and used gene targeting to generate mice lacking tensin. Even though tensin is expressed in many different tissues duri ng embryogenesis, tensin null mice developed normally and appeared hea lthy postnatally for at least several months. Over time, -/- mice beca me frail because of abnormalities in their kidneys, an organ that expr esses high levels of tensin. Mice with overt signs of weakness exhibit ed signs of renal failure and possessed multiple large cysts in the pr oximal kidney tubules, but even in tensin null mice with normal blood analysis, cysts were prevalent. Ultrastructurally, noncystic areas sho wed typical cell-matrix junctions that readily labeled with antibodies against other focal adhesion molecules. In abnormal regions, cell-mat rix junctions were disrupted and tubule cells lacked polarity. Taken t ogether, our data imply that, in the kidney, loss of tensin leads to a weakening, rather than a severing, of focal adhesion. All other tissu es appeared normal, suggesting that, in most cases, tensin's diverse f unctions are redundant and may be compensated for by other focal adhes ion proteins.