Disorganization (Ds), a single gene mouse mutation, has profound effects on mouse development. Unlike most mutations where particular traits with diagnostic features are inherited among generations, the heritable trait in mice with the Ds mutation is the propensity for the body to be formed in an unpredictable manner. No two mice are affected in identical ways. Affected mice may show agenesis, duplication or fusion of structures, and all morphological structures seem prone to anomaly. Remarkably, these mice are not prone to cancer, spotting, behavior, and longevity or fertility problems. Ds is one of the few examples in mammals of a true dominant, gain-of-function mutation. Determining the identity of the Ds gene is important because deep insights into the regulation of pattern formation during development can be gained. In addition, insights into the molecular nature of mutations that show variable expression and low penetrance may be forthcoming. Ds has been located to a 0.2 cM segment of mouse Chr 14, cloned in a 360 kb BAC contig and 80 kb of sequence has been obtained. Cloning of the mouse Ds gene is proposed. The genomic sequence of the Ds locus will be determined in wild-type mice in order to identify genes and markers, evidence for rearrangement in Ds will be sought, cDNA expression and sequence will be assessed in wild type and Ds mice, and the genomic sequence of the Ds locus will be determined. In addition, it is proposed that the identity of Ds will be verified by generation and characterization of transgenic mice with the candidate Ds mutation.
|Colvin, J S; Feldman, B; Nadeau, J H et al. (1999) Genomic organization and embryonic expression of the mouse fibroblast growth factor 9 gene. Dev Dyn 216:72-88|