Human Molecular Genetics Advance Access published online on March 17, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh116
© 2004 by Oxford University Press
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1 Departments of Pediatrics and Medicine, UCSD Cancer Center, University of California, San Diego School of Medicine, 9500 Gilman Drive, Mailstop 0627, La Jolla, CA 92093-0627
* To whom correspondence should be addressed. E-mail: awynshawboris{at}ucsd.edu.
The Mnt gene encodes a Mad-family bHLH transcription factor located on human 17p13.3. Mnt is one of twenty genes deleted in a heterozygous fashion in Miller-Dieker syndrome (MDS), a contiguous gene syndrome that consists of severe neuronal migration defects and craniofacial dysmorphic features. Mnt can inhibit Myc-dependent cell transformation and is hypothesized to counterbalance the effects of c-Myc on growth and proliferation in vivo by competing with Myc for binding to Max and by repressing target genes activated by Myc:Max heterodimers. Unlike the related Mad family members, Mnt is expressed ubiquitously and Mnt/Max heterodimers are found in proliferating cells that contain Myc/Max heterodimers, suggesting a unique role for Mnt during proliferation. To examine the role of Mnt in vivo, we produced mice with null (MntKO) and loxP-flanked conditional knock-out (MntCKO) alleles of Mnt. Virtually all MntKO/KO mutants in a mixed (129S6 x NIH Black Swiss) or inbred (129S6) genetic background died perinatally. Mnt-deficient embryos exhibited small size throughout development and showed reduced levels of c-Myc and N-Myc. In addition, 37% of the mixed background mutants displayed cleft palate as well as retardation of skull development, a phenotype not observed in the inbred mutants. These results demonstrate an important role for Mnt in embryonic development and survival, and suggest that Mnt may play a role in the craniofacial defects displayed by MDS patients.
Article
Loss of the Max-interacting protein Mnt in mice results in decreased viability, defective embryonic growth and craniofacial defects: relevance to Miller-Dieker syndrome
2 Center for Genome Medical Science, Saitama Medical School, PRESTO, Japan Science and Technology Corporation, Inariyama 1397-1 Yamane, Hidaka City, Saitama 350-1241, Japan
3 Departments of Pediatrics and Medicine, UCSD Cancer Center, University of California, San Diego School of Medicine, 9500 Gilman Drive, Mailstop 0627, La Jolla, CA 92093-0627; Present addresses: Department of Pediatrics, Division of Medical Genetics, The University of Texas Health Science Center at Houston Medical School, Houston, TX 77030
4 Shriners Hospitals for Children, Department of Cell and Developmental Biology, Oregon Health Sciences University, 3101 S.W. Sam Jackson Park Rd., Portland, OR 97201
5 Department of Medicine, Howard Hughes Medical Institute, University of California, San Diego School of Medicine, 9500 Gilman Drive, Mailstop 0627, La Jolla, CA 92093-0627
6 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, North-Mailstop A2-025, P.O. Box 19024, Seattle, Washington 98109-1024
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