Characterization of the Murine mafF Gene*
- Ko Onodera‡,
- Jordan A. Shavit‡,
- Hozumi Motohashi§,
- Fumiki Katsuoka§,
- Jun-etsu Akasaka§,
- James Douglas Engelঠand
- Masayuki Yamamoto§
- From the ‡Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston Illinois 60208-3500 and §Institute of Basic Medical Sciences and Center for TARA, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305, Japan
Abstract
Small Maf proteins are obligatory heterodimeric partner molecules of mammalian Cap’n’Collar proteins that together control a wide variety of eukaryotic genes. Although both MafK and MafG are expressed in overlapping but distinct tissue distribution patterns during embryonic development, the physiological consequences of loss-of-function mutations in either gene are modest. This suggested that compensation by the third small Maf protein, MafF, might be a major reason for such mild phenotypes and that further analysis of MafF might therefore provide important insights for understanding small Maf regulatory function(s). We therefore cloned, mapped, transcriptionally and developmentally characterized, and finally disrupted themafF gene. We show that murine mafF is transcriptionally regulated by three different promoters and is most abundantly expressed in the lung. The lacZ gene inserted into the mafF locus revealed prominent expression sites in the gut, lung, liver, outflow tract of the heart, cartilage, bone membrane, and skin but not in hematopoietic cells at any developmental stage. Homozygous mafF null mutant mice were born in a normal Mendelian ratio and displayed no obvious functional deficiencies, indicating that MafF activity may be dispensable even in tissues where the expression of other small Maf proteins is quite low.
Footnotes
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↵* This work was supported by fellowships from the Japan Society for the Promotion of Science (to K. O.) and National Institutes of Health (NIH) Medical Scientist Training Program Grant GM08152 to Northwestern University (to J. A. S.). Research support was provided by the Japanese Ministry of Education, Science, and Culture, CREST, and JSPS as well as core facility support from Robert H. Lurie Comprehensive Cancer Center Grant CA60553 and NIH Grant CA80088 (to J. D. E.).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.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) and .
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↵¶ To whom correspondence should be addressed: Depts. of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University 2153 N. Campus Dr., Evanston, IL 60208-3500. Tel.: 847-491-5139; Fax: 847-467-2152; E-mail: d-engel@nwu.edu.
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↵3 K. Onodera, J. A. Shavit, H. Motohashi, F. Katsuoka, J. Akasaka, J. D. Engel, and M. Yamamoto, our unpublished observations.
- Abbreviations:
- CNC
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Cap’n’Collar protein
- ES
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embryonic stem cells
- RACE
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5′-rapid amplification of cDNA ends
- kbp
-
kilobase pair(s)
- nls
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nuclear localization signal
- RT-PCR
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reverse transcription-polymerase chain reaction
- dpc
-
days post-coitus
- RFLP
-
restriction fragment length polymorphism
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- Received March 22, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
