| First Author | Reed V | Year | 1998 |
| Journal | 12th International Mouse Genome Conference 9/29/98 - 10/3/98, Garmisch-Pastenkerchen, Germany | Pages | E24 (Abstr.) |
| Mgi Jnum | J:50325 | Mgi Id | MGI:1309900 |
| Citation | Reed V, et al. (1998) Characterisation of X-linked developmental mutants with craniofacial abnormalities. 12th International Mouse Genome Conference 9/29/98 - 10/3/98, Garmisch-Pastenkerchen, Germany :E24 (Abstr.) |
| abstractText | Full text of Abstract: E24. CHARACTERISATION OF X-LINKED DEVELOPMENTAL MUTANTS WITH CRANIOFACIAL ABNORMALITIES. Vivienne Reed, Emmanuelle Gormally, Walter Masson, Terry Hacker, Yvonne Boyd. MRC Mammalian Genetics Unit, Harwell, Oxfordshire, England. In man, malformations of the face and skull occur with a frequency of >1 in 1000 live births. However, sparse pedigree data and genetic heterogeneity often complicate molecular genetic analysis and can cause major problems in clinical classification, and hence prognosis. It is possible to exploit single gene mutations in the mouse which are known to affect head morphology, to clone and characterise novel genes involved in craniofacial malformations. We are currently studying two X-linked semidominant phenotypes (tattered and broad-headed) and one X-linked recessive phenotype (wide-faced) to identify novel genes involved in head development. Heterozygous females have patchy hyperkeratotic skin and have an abnormal head morphology. Tattered males die between mid and late gestation and examination of affected embryos revealed abnormalities in craniofacial, limb and intestinal development. We have localised the tattered gene (Td) to a <0.2cM interval between Tcfe3 and DXHXS7465e in the proximal region ot the mouse X chromosome. Broad-headed (Bhd) males die within a few hours of birth possibly due to asphyxiation resulting from skeletal abnormalities in the head and neck regions. We have positioned Bhd dose to Zfx in the DXMit45 to DXMit16 region using two high resolution intraspecific backcrosses. Wide-faced (wf) males and homozygous females have a similar craniofacial appearance to heterozygous broad-headed females but are fully viable. In an intraspecific backcross, wf cosegregates with DXMit50 which lies distal to Agtr2 on the mouse X chromosome. The cloning and characterisation of genes implicated in the craniofacial malformations present in these three X-linked mouse mutants will allow identification of potentially homologous human syndromes. The characterization of these genes will also increase understanding of the process of mammalian skull development and of the molecular signals involved in bone formation. |
