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* Department of Cell Biology and Anatomy, Faculty of Medicine, University of Tokyo, Tokyo, 113, Japan; and Microtubule-associated protein 1B
(MAP1B), one of the microtubule-associated proteins
(MAPs), is a major component of the neuronal cytoskeleton. It is expressed at high levels in immature neurons during growth of their axons, which indicates that
it plays a crucial role in neuronal morphogenesis and
neurite extension. To better define the role of MAP1B
in vivo, we have used gene targeting to disrupt the murine MAP1B gene. Heterozygotes of our MAP1B disruption exhibit no overt abnormalities in their development and behavior, while homozygotes showed a
slightly decreased brain weight and delayed nervous
system development. Our data indicate that while
MAP1B is not essential for survival, it is essential for
normal time course development of the murine nervous
system. These conclusions are very different from those
of a previous MAP1B gene-targeting study (Edelmann,
W., M. Zervas, P. Costello, L. Roback, I. Fischer, A. Hammarback, N. Cowan, P. Davis, B. Wainer, and R. Kucherlapati. 1996. Proc. Natl. Acad. Sci. USA. 93:
1270-1275). In this previous effort, homozygotes died
before reaching 8-d embryos, while heterozygotes
showed severely abnormal phenotypes in their nervous
systems. Because the gene targeting event in these mice
produced a gene encoding a 571-amino acid truncated product of MAP1B, it seems likely that the phenotypes
seen arise from the truncated MAP1B product acting in
a dominant-negative fashion, rather than a loss of
MAP1B function.
Department of
Cell Biology, Cancer Institute, Tokyo, 170, Japan
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