Molecular analysis of radiation-induced albino (c)-locus mutations that cause death at preimplantation stages of development.

Abstract

Deletion mutations at the albino (c) locus have been useful for continuing the development of fine-structure physical and functional maps of the Fes-Hbb region of mouse chromosome 7. This report describes the molecular analysis of a number of radiation-induced c deletions that, when homozygous, cause death of the embryo during preimplantation stages. The distal extent of these deletions defines a locus, pid, (preimplantation development) genetically associated with this phenotype. The proximal breakpoints of eight of these deletions were mapped with respect to the Tyr (tyrosinase; albino) gene as well as to anonymous loci within the Fah-Tyr region that are defined by the Pmv-31 viral integration site and by chromosome-microdissection clones. Rearrangements corresponding to the proximal breakpoints of two of these deletions were detected by Southern blot analysis, and a size-altered restriction fragment carrying the breakpoint of one of them was cloned. A probe derived from this deletion fusion fragment defines a locus, D7Rn6, which maps 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 region and to loci mapping distal to pid that are defined by N-ethyl-N-nitrosourea-induced lethal mutations.

Molecular genetics of the brown (b)-locus region of mouse chromosome 4. II. Complementation analyses of lethal brown deletions.

“…This type of strategy has been successful in subdividing a series of prenatally lethal albino (c)-locus deletions into those that cause death during preimplantation development when homozygous us. those that cause death shortly after implantation (RUSSELL and RAYMER 1979;RUSSELL et al 1982;RINCHIK et al 1993a). This type of strategy has also been successful in subdividing the series of postimplantation lethal cdeletions and has provided evidence for at least two loci (necessary for extraembryonic and embryonic ectoderm development, respectively), by identifylng deletions that included either the latter locus or both loci (NISWANDER et al 1989).…”