This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Meester-Smoor, M. A.
Right arrow Articles by Zwarthoff, E. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meester-Smoor, M. A.
Right arrow Articles by Zwarthoff, E. C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2005, p. 4229-4236, Vol. 25, No. 10
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.10.4229-4236.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Targeted Disruption of the Mn1 Oncogene Results in Severe Defects in Development of Membranous Bones of the Cranial Skeleton

Magda A. Meester-Smoor,1 Marcel Vermeij,1 Marjolein J. L. van Helmond,1 Anco C. Molijn,1,{dagger} Karel H. M. van Wely,1,{ddagger} Arnold C. P. Hekman,1 Christl Vermey-Keers,2 Peter H. J. Riegman,1 and Ellen C. Zwarthoff1*

Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands,1 Department of Plastic and Reconstructive Surgery, Erasmus MC, Rotterdam, The Netherlands2

Received 23 November 2004/ Accepted 26 February 2005

Fusion of the MN1 gene to TEL (ETV6) results in myeloid leukemia. The fusion protein combines the transcription activating domain of MN1 and the DNA binding domain of TEL and is thought to act as a deranged transcription factor. In addition, disruption of the large first exon of the MN1 gene is thought to inactivate MN1 function in a meningioma. To further investigate the role of MN1 in cancer, we generated Mn1 knockout mice. Mn1+/– animals were followed for 30 months, but they had no higher incidence of tumor formation than wild-type littermates. Mn1 null mice, however, were found to die at birth or shortly thereafter as the result of a cleft palate. Investigation of newborn or embryonic day 15.5 (E15.5) to E17.5 null mice revealed that the development of several bones in the skull was abnormal. The affected bones are almost exclusively formed by intramembranous ossification. They are either completely agenic at birth (alisphenoid and squamosal bones and vomer), hypoplastic, deformed (basisphenoid, pterygoid, and presphenoid), or substantially thinner (frontal, parietal, and interparietal bones). In heterozygous mice hypoplastic membranous bones and incomplete penetrance of the cleft palate were observed. We conclude that Mn1 is an important factor in development of membranous bones.

* Corresponding author. Mailing address: Erasmus MC, Department of Pathology, Josephine Nefkens Institute, room Be300b, P.O. box 1738, 3000 DR Rotterdam, The Netherlands. Phone: 31 (0) 10 4087929. Fax: 31 (0) 10 4089487. E-mail: e.zwarthoff{at}erasmusmc.nl.

{dagger} Present address: Delft Diagnostic Laboratories, Delft, The Netherlands.

{ddagger} Present address: Department of Immunology and Oncology, Centro Nacional de Biotechnologia, Madrid, Spain.

Molecular and Cellular Biology, May 2005, p. 4229-4236, Vol. 25, No. 10
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.10.4229-4236.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhang, X., Dowd, D. R., Moore, M. C., Kranenburg, T. A., Meester-Smoor, M. A., Zwarthoff, E. C., MacDonald, P. N. (2009). Meningioma 1 Is Required for Appropriate Osteoblast Proliferation, Motility, Differentiation, and Function. J. Biol. Chem. 284: 18174-18183 [Abstract] [Full Text]  
  • Meng, L., Bian, Z., Torensma, R., Von den Hoff, J.W. (2009). Biological Mechanisms in Palatogenesis and Cleft Palate. JDR 88: 22-33 [Abstract] [Full Text]  
  • Liu, W., Lan, Y., Pauws, E., Meester-Smoor, M. A., Stanier, P., Zwarthoff, E. C., Jiang, R. (2008). The Mn1 transcription factor acts upstream of Tbx22 and preferentially regulates posterior palate growth in mice. Development 135: 3959-3968 [Abstract] [Full Text]  
  • Heuser, M., Argiropoulos, B., Kuchenbauer, F., Yung, E., Piper, J., Fung, S., Schlenk, R. F., Dohner, K., Hinrichsen, T., Rudolph, C., Schambach, A., Baum, C., Schlegelberger, B., Dohner, H., Ganser, A., Humphries, R. K. (2007). MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA resistance in patients with AML. Blood 110: 1639-1647 [Abstract] [Full Text]  
  • Meester-Smoor, M. A, Molijn, A. C, Zhao, Y., Groen, N. A, Groffen, C. A H, Boogaard, M., van Dalsum-Verbiest, D., Grosveld, G. C, Zwarthoff, E. C (2007). The MN1 oncoprotein activates transcription of the IGFBP5 promoter through a CACCC-rich consensus sequence. J Mol Endocrinol 38: 113-125 [Abstract] [Full Text]  
  • Heuser, M., Beutel, G., Krauter, J., Dohner, K., von Neuhoff, N., Schlegelberger, B., Ganser, A. (2006). High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. Blood 108: 3898-3905 [Abstract] [Full Text]  
  • Sutton, A. L. M., Zhang, X., Ellison, T. I., MacDonald, P. N. (2005). The 1,25(OH)2D3-Regulated Transcription Factor MN1 Stimulates Vitamin D Receptor-Mediated Transcription and Inhibits Osteoblastic Cell Proliferation. Mol. Endocrinol. 19: 2234-2244 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»