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The Journal of Neuroscience, January 1, 1998, 18(1):284-293
Mouse Zic1 Is Involved in Cerebellar Development
Jun Aruga1, Osamu Minowa2, Hiroyuki Yaginuma3, Junko Kuno2, Takeharu Nagai1, Tetsuo Noda2, and Katsuhiko Mikoshiba1, 4, 5 1 Molecular Neurobiology Laboratory, Tsukuba Life Science Center and Brain Science Institute, Institute of Physical and Chemical Research (RIKEN), Tsukuba, Ibaraki 305, Japan, 2 Department of Cell Biology, Cancer Institute, Tokyo 170, Japan, 3 Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305, Japan, 4 ; Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Tokyo 108, Japan, and 5 Calciosignal Net Project, Exploratory Research for Advanced Technology, Tokyo 153, Japan
Zic genes encode zinc finger proteins, the expression of which is highly restricted to cerebellar granule cells and their precursors. These genes are homologs of the Drosophila pair-rule gene odd-paired. To clarify the role of the Zic1 gene, we have generated mice deficient in Zic1. Homozygous mice showed remarkable ataxia during postnatal development. Nearly all of the mice died within 1 month. Their cerebella were hypoplastic and missing a lobule in the anterior lobe. A bromodeoxyuridine labeling study indicated a reduction both in the proliferating cell fraction in the external germinal layer (EGL), from 14 d postcoitum, and in forward movement of the EGL. These findings suggest that Zic1 may determine the cerebellar folial pattern principally via regulation of cell proliferation in the EGL.
Key words: Zic1; transcription factor; cerebellum; granule cell; cerebellar foliation; ataxia; gene targeting
Copyright © 1998 Society for Neuroscience 0270-6474/98/181284-10$05.00/0
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