A new spontaneous mutation (tuft) causing defective neuropore closure and craniofacial lipoma maps to proximal chromosome 10 in the 3H1 mouse

Neural tube defects occur when the anterior or posterior neuropore fail to close. Numerous genes associated with neural tube closure have been identified. A spontaneous mutation, characterized by a midline cranial lipoma, arose in a 3H1 inbred mouse strain housed at the University of Hawaii. The purpose of this study was to: 1) undertake a histochemical analysis of the lipoma to determine whether the tumor could be characterized as a meningioma; and 2) perform a genomic scan to identify the chromosome associated with the mutation. Affected adult 3H1 mice were anesthetized with 1% avertin, perfused with 4% paraformaldehyde, the brain was resected and cryostat sectioned, and stained with either vimentin or epithelial membrane antigen (EMA). An interspecific backcross strategy was employed and DNA samples extracted from tail tissue were analyzed for linkage with microsatellite markers dispersed throughout the genome. The lipoma stained negatively for both vimentin and EMA indicating that the tumor could not be classified as a meningioma. The mapping analysis showed recombination rates of 16% on chromosome 10 and localized to a region 38.4 cM from the centromere. This region has not been previously reported to be associated with neural tube defects. These data suggest that the tuft mutation probably arises early in development with the incorporation of mesoderm into the neuropore, eventually resulting in a lipoma.