MOLECULAR ANALYSIS OF RADIATION-INDUCED ALBINO (C)-LOCUS MUTATIONS THAT CAUSE DEATH AT PREIMPLANTATION STAGES OF DEVELOPMENT

Deletion mutations at the albino (c) locus have been useful for contin uing the development of finestructure physical and functional maps of the Fes-Hbb region of mouse chromosome 7. This report describes the mo lecular analysis of a number of radiation-induced c deletions that, wh en homozygous, cause death of the embryo during preimplantation stages . The distal extent of these deletions defines a locus, pid, (preimpla ntation development) genetically associated with this phenotype. The p roximal breakpoints of eight of these deletions were mapped with respe ct to the Tyr (tyrosinase; albino) gene as well as to anonymous loci w ithin the Fah-Tyr region that are defined by the Pmv-31 viral integrat ion site and by chromosome-microdissection clones. Rearrangements corr esponding to the proximal breakpoints of two of these deletions were d etected by Southern blot analysis, and a size-altered restriction frag ment carrying the breakpoint of one of them was cloned. A probe derive d from this deletion fusion fragment defines a locus, D7Rn6, which map s within (or distal to) the pid region, and which discriminates among the distal extents of deletions eliciting the pid phenotype. Extension of physical maps from D7Rn6 should provide access both to the pid reg ion and to loci mapping distal to Pid that are defined by N-ethyl-N-ni trosourea-induced lethal mutations.