Journal 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
Human molecular genetics, v 13(10), pp 1057-1067
15 May 2004
PMID: 15028671
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 (129S6×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.
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Details
- Title
- Loss of the Max-interacting protein Mnt in mice results in decreased viability, defective embryonic growth and craniofacial defects: relevance to Miller–Dieker syndrome
- Creators
- Kazuhito Toyo-oka - University of California San DiegoShinji Hirotsune - Saitama Medical UniversityMichael J. Gambello - The University of Texas Health Science Center at HoustonZi-Qiang Zhou - Oregon Health & Science UniversityLorin Olson - University of California San DiegoMichael G. Rosenfeld - University of California San DiegoRobert Eisenman - Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South AfricaPeter Hurlin - Oregon Health & Science UniversityAnthony Wynshaw-Boris - University of California San Diego
- Publication Details
- Human molecular genetics, v 13(10), pp 1057-1067
- Publisher
- Oxford University Press
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000221142700007
- Scopus ID
- 2-s2.0-2542536778
- Other Identifier
- 991020100194604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Genetics & Heredity