| First Author | Raymond S | Year | 1994 |
| Journal | Genet Res | Volume | 63 |
| Issue | 2 | Pages | 155 (Abstr) |
| Mgi Jnum | J:18590 | Mgi Id | MGI:66853 |
| Citation | Raymond S, et al. (1994) Molecular characterization of the mouse Bw mutation causing premature melanocyte death - melanocytes and early development. Genet Res 63(2):155 (Abstr) |
| abstractText | Full text of Abstract: Molecular characterization of the mouse Bw mutation causing premature melanocyte death - melanocytes and early development. SOPHIE RAYMOND AND IAN J. JACKSON. MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland White-based brown (Bw) is a dominant mutant allele of the mouse brown locus on chromosome 4 which results in hairs being pigmented only at their tips. This phenotype is due to premature melanocyte death. Southern plot analysis revealed a large rearrangement in the first intron of the tyrosinase related protein 1 (TRP-1) gene encoded at the brown locus. Bw specific probes were derived by inverse PCR on Bw/Bw genomic DNA using TRP-1 primers upstream and downstream of the rearrangement. Molecular analysis showed that the Bw rearrangement is a large chromosomal inversion. Since the mutation is dominant and its effect seems to be restricted to melanocytes, a likely hypothesis is that the inversion brings a 'toxic' gene under the control of previously characterized melanocyte specific transcription regulating elements (MSE) which direct TRP-1 expression in the wild-type mouse. To identify this gene, we have isolated lambda clones from a wild-type mouse genomic library, which map downstream of the TRP-1 MSE in Bw. A 6.5 kbp plasrnid subclone mapping at the 5' end of the inversion was used to probe zoo blots and a strong cross-species hybridization was observed with mammalian genomic DNAs suggesting the presence of a conserved gene downstream of the inversion breakpoint. The normal function of this gene and the mechanism by which it kills melanocytes will be of interest. In order to study the role of melanocytes much earlier in development, we are generating lines of transgenic mice for which the melanocyte lineage is ablated by a toxigenic construct. Our approach and first results will be presented. |
