© The Rockefeller University Press,
0021-9525/1997//1615 $5.00
The Journal of Cell Biology, Volume 137, Number 7,
, 1997 1615-1626
Delayed Development of Nervous System in Mice Homozygous for Disrupted Microtubule-associated Protein 1B (MAP1B) Gene
Yosuke Takei*,
Satoru Kondo*,
Akihiro Harada*,
Satomi Inomata*,
Tetsuo Noda
, and
Nobutaka Hirokawa*
* Department of Cell Biology and Anatomy, Faculty of Medicine, University of Tokyo, Tokyo, 113, Japan; and
Department of Cell Biology, Cancer Institute, Tokyo, 170, Japan
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.
1. Abbreviations used in this paper: ES, embryonic stem; LC, light chain; MAP, microtubule-associated protein; MT, microtubule; NF, neurofilament.
Address all correspondence to N. Hirokawa, Department of Cell Biology and Anatomy, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113, Japan. Tel.: 81-3-3812-2111 ext. 3326. Fax: 81-3-5689-4856.

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