Regulation of Lens Fiber Cell Differentiation by Transcription Factor c-Maf*
- Shimako Kawauchiद,
- Satoru Takahashi‡,
- Osamu Nakajima‡,
- Hajime Ogino¶,
- Masanobu Morita‡,
- Makoto Nishizawa‖,
- Kunio Yasuda¶ and
- Masayuki Yamamoto‡**
- From the ‡Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305-8577, §Graduate School of Dentistry, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan, ¶Nara Institute of Science and Technology, Ikoma 630-0101, Japan, and ‖Scripps Research Institute, La Jolla, California 92037
Abstract
To elucidate the regulatory mechanisms underlying lens development, we searched for members of the large Maf family, which are expressed in the mouse lens, and found three, c-Maf, MafB, and Nrl. Of these, the earliest factor expressed in the lens was c-Maf. The expression of c-Maf was most prominent in lens fiber cells and persisted throughout lens development. To examine the functional contribution of c-Maf to lens development, we isolated genomic clones encompassing the murine c-maf gene and carried out its targeted disruption. Insertion of the β-galactosidase (lacZ) gene into the c-maf locus allowed visualization of c-Maf accumulation in heterozygous mutant mice by staining for LacZ activity. Homozygous mutant embryos and newborns lacked normal lenses. Histological examination of these mice revealed defective differentiation of lens fiber cells. The expression of crystallin genes was severely impaired in the c-maf-null mutant mouse lens. These results demonstrate that c-Maf is an indispensable regulator of lens differentiation during murine development.
Footnotes
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↵* This work was supported in part by grants-in-aid from the Ministry of Education, Science, Sports, and Culture, Core Research for Evolutional Sciences and Technology, and the Japanese Society for Promotion of Sciences.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
This paper is dedicated to the memory of Dr. Kazuhiko Umesono, whose life work was dedicated to elucidating the multiple facets of transcription factor research.
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↵** To whom correspondence should be addressed: Center for TARA, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan. Tel.: 81-298-53-6158; Fax: 81-298-53-7318; E-mail: masi{at}tara.tsukuba.ac.jp.
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↵2 H. Ogino and K. Yasuda, unpublished observation.
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↵3 K. Yasuda, unpublished observation.
- Abbreviations:
- MARE
-
Maf responsive element
- ES
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embryonic stem
- ORF
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open reading frame
- LacZ
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Escherichia coli β-galactosidase gene
- 5′-RACE
-
5′-rapid amplification of the cDNA end
- RT-PCR
-
reverse transcriptase-polymerase chain reaction
- DT-A
-
diphtheria toxin A
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- Received February 3, 1999.
- Revision received March 22, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
