title: Targeted disruption of the Mn1 oncogene results in severe defects in development of membranous bones of the cranial skeleton.
abstract: 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.
authors.affiliation: Erasmus MC, Department of Pathology, Josephine Nefkens Institute, Rotterdam, The Netherlands.
authors.forename: Magda A
authors.initials: MA
authors.lastname: Meester-Smoor
authors.forename: Marcel
authors.initials: M
authors.lastname: Vermeij
authors.forename: Marjolein J L
authors.initials: MJ
authors.lastname: van Helmond
authors.forename: Anco C
authors.initials: AC
authors.lastname: Molijn
authors.forename: Karel H M
authors.initials: KH
authors.lastname: van Wely
authors.forename: Arnold C P
authors.initials: AC
authors.lastname: Hekman
authors.forename: Christl
authors.initials: C
authors.lastname: Vermey-Keers
authors.forename: Peter H J
authors.initials: PH
authors.lastname: Riegman
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002972:Cleft Palate / Q000235:genetics; D017353:Gene Deletion; D006257:Head / Q000002:abnormalities / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D008136:Longevity / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D012886:Skull / Q000002:abnormalities* / Q000196:embryology / Q000254:growth & development* / Q000473:pathology; D016019:Survival Analysis; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins
chemical_list: C501081:Mn1 protein, mouse; D015513:Oncogene Proteins; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins