THE tau gene encodes a protein (Tau) that is a major neuronal microtub
ule-associated protein localized mostly in axons(1-4). It has microtub
ule-binding and tubulin-polymerizing activity in vitro(3,4) and is tho
ught to make short crossbridges between axonal microtuhules(5,6). Furt
her, tau-transfected non-neuronal cells extend long axon-like processe
s in which microtubule bundles resembling those in axons are formed(6-
8). In contrast, tau antisense oligonucleotides selectively suppress a
xonal elongation in cultured neurons(9,10). Thus tau is thought to be
essential for neuronal cell morphogenesis, especially axonal elongatio
n and maintenance. To test this hypothesis, we used gene targeting to
produce mice lacking the tau gene. We show that the nervous system of
tau-deficient mice appears to be normal immunohistologically. Furtherm
ore, axonal elongation is not affected in cultured neurons. But in som
e small-calibre axons, microtubule stability is decreased and microtub
ule organization is significantly changed. We observed an increase in
microtubule-associated protein 1A which may compensate for the functio
ns of tau in large-calibre axons. Our results argue against the sugges
ted role of tau in axonal elongation but confirm that it is crucial in
the stabilization and organization of axonal microtubules in a certai
n type of axon.