Production and Analysis of Mice Deficient in Microtubule-Associated-Protein Tau

Abstract

Considerable evidence supports the hypothesis that tau, one of the major neuronal microtubule-associated proteins (MAPs), is essential for neuronal cell morphogenesis and axonal maintenance. To examine this hypothesis in detail, we have produced mice lacking tau. Surprisingly, tau-deficient mice were viable and fertile. Histological and immunocytochemical examination of the nervous system in general revealed no abnormalities throughout development. Furthermore, selective axonal elongation was not affected in cultured neurons. We observed increase in another MAP which may partially compensate for the loss of tau. However, in some small caliber axons, decrease in microtubule (MT) stability was observed and MP organization was significantly changed. Our results argue against the hypothesized role of tau in neuronal cell morphogenesis but support its crucial role in the stabilization and organization of axonal MTs in a certain type of axons.