International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


Bogani D 1, Willoughby C 1, Mirza G 2, Davies J 1, Ragoussis I 2, Arkell R 1

1 Mammalian Genetics Unit, Medical Research Council, Harwell, Didcot, United Kingdom, 2 Wellcome Trust Centre for Human Genetics, Department of Genomics, Oxford, United States

Holoprosencephaly (HPE) is a relatively common developmental defect of the forebrain and often the midface in humans that can be due to both genetic and environmental causes and involves incomplete development and septation of midline structures of the central nervous system. HPE has a prevalence of 1:250 during embryogenesis and, due to lethality, of 1:16000 newborn infants. During a screen for recessive mutations at a defined region of mouse chromosome 13 (Del(13)Svea36H) we have isolated several mutants that exhibit HPE as their main embryonic phenotype. The phenotype is frequently visible at 9.5 dpc and represented by the typical reduction of the distance between sagittally symmetrical structures of the forebrain (optic vesicles, etc.). Monozygosity for the telomeric region of human 6p, largely syntenic with Del(13)Svea36H, has been associated with HPE in aborted foetuses amongst other craniofacial and congenital abnormalities. This points to a new HPE locus in humans and to the possibility that the mutated gene in our mutant lines is the mouse homologue. Recombination mapping results indicate that at least 3 mutations map to overlapping regions of Del(13)Svea36H. Complementation testing and further mapping will confirm whether the mutated gene is the same in these lines. Mutation detection in candidate genes is also being carried out together with more detailed phenotypic analysis. Results of these experiments will be presented.

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