Human molecular genetics, vol. 13(10), 2004, pp. 1057-1067
Department of Neurobiology and Anatomy
Drexel University College of Medicine
2900 W. Queen Lane, Room186
Toyo-oka, K., Hirotsune, S., Gambello, M., Zhou, Z.-Q., Olson, L. E., Rosenfeld, M., … Wynshaw-Boris, A. (2004). 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, 13(10), 1057–1067.
Toyo-oka, K., S. Hirotsune, M. Gambello, Zi-Qiang Zhou, Lorin E. Olson, M. Rosenfeld, R. Eisenman, P. Hurlin, and A. Wynshaw-Boris. “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 13, no. 10 (2004): 1057–1067.
Toyo-oka, K., et al. “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, vol. 13, no. 10, 2004, pp. 1057–67.
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 (Mnt(KO)) and loxP-flanked conditional knock-out (Mnt(CKO)) alleles of Mnt. Virtually all Mnt(KO/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.