Skip Navigation


Human Molecular Genetics Advance Access originally published online on March 17, 2004
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
13/10/1057    most recent
ddh116v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (21)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Toyo-oka, K.
Right arrow Articles by Wynshaw-Boris, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Toyo-oka, K.
Right arrow Articles by Wynshaw-Boris, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2004, Vol. 13, No. 10 1057-1067
DOI: 10.1093/hmg/ddh116
Human Molecular Genetics, Vol. 13, No. 10 © Oxford University Press 2004; all rights reserved

Loss of the Max-interacting protein Mnt in mice results in decreased viability, defective embryonic growth and craniofacial defects: relevance to Miller–Dieker syndrome

Kazuhito Toyo-oka1, Shinji Hirotsune2, Michael J. Gambello1,{dagger}, Zi-Qiang Zhou3, Lorin Olson4, Michael G. Rosenfeld4, Robert Eisenman5, Peter Hurlin3 and Anthony Wynshaw-Boris1,*

1Departments 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, USA, 2Center for Genome Medical Science, Saitama Medical School, PRESTO, Japan Science and Technology Corporation, Saitama, Japan, 3Shriners Hospitals for Children, Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, OR, USA, 4Department of Medicine, Howard Hughes Medical Institute, University of California, La Jolla, CA, USA and 5Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

Received January 20, 2004; Accepted March 9, 2004

The Mnt gene encodes a Mad-family bHLH transcription factor located on human 17p13.3. Mnt is one of 20 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 (129S6xNIH 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.

* To whom correspondence should be addressed. Tel: +1 8588223400; Fax: +1 8588223409; Email: awynshawboris{at}ucsd.edu


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 JDRHome page
L. Meng, Z. Bian, R. Torensma, and J.W. Von den Hoff
Biological Mechanisms in Palatogenesis and Cleft Palate
Journal of Dental Research, January 1, 2009; 88(1): 22 - 33.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Toyo-oka, T. J. Bowen, S. Hirotsune, Z. Li, S. Jain, S. Ota, L. E. Lozach, I. G. Bassett, J. Lozach, M. G. Rosenfeld, et al.
Mnt-Deficient Mammary Glands Exhibit Impaired Involution and Tumors with Characteristics of Myc Overexpression
Cancer Res., June 1, 2006; 66(11): 5565 - 5573.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. Dezfouli, A. Bakke, J. Huang, A. Wynshaw-Boris, and P. J. Hurlin
Inflammatory disease and lymphomagenesis caused by deletion of the myc antagonist mnt in T cells.
Mol. Cell. Biol., March 1, 2006; 26(6): 2080 - 2092.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
C. W. Hooker and P. J. Hurlin
Of Myc and Mnt
J. Cell Sci., January 15, 2006; 119(2): 208 - 216.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
L. W. M. Loo, J. Secombe, J. T. Little, L.-S. Carlos, C. Yost, P.-F. Cheng, E. M. Flynn, B. A. Edgar, and R. N. Eisenman
The Transcriptional Repressor dMnt Is a Regulator of Growth in Drosophila melanogaster
Mol. Cell. Biol., August 15, 2005; 25(16): 7078 - 7091.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
W. Walker, Z.-Q. Zhou, S. Ota, A. Wynshaw-Boris, and P. J. Hurlin
Mnt-Max to Myc-Max complex switching regulates cell cycle entry
J. Cell Biol., May 9, 2005; 169(3): 405 - 413.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.