Genetic analysis of the exed region in mouse

The extraembryonic ectoderm development (exed) mutant phenotype was described in mice homozygous for the c(6H) deletion, a radiation-induced deletion in the tyrosinase region of mouse Chromosome 7. These mutants fail to gastrulate and die around embryonic day 8.0. Several genes including, for example, embryonic ectoderm development (eed), are deleted in the c(6H) mutants; however, the portion of the chromosome responsible for the more severe exed phenotype is localized to a 20-kb region called the "exed-critical region." To understand the genetics behind the exed phenotype, we analyzed this region in two ways. First, to determine whether the 20-kb exed-critical region alone causes the mutant phenotype, we removed it from a wild-type chromosome. The resulting mice homozygous for this deletion were viable and fertile, indicating that the 20-kb exed-critical region by itself is not sufficient to cause the phenotype when deleted. We then sequenced the 20-kb exed-critical region and no expressed exons were found. Several short matches to GenBank Expressed Sequence Tag (EST) databases were identified; however, none of these ESTs mapped to the region. Taken together, these results indicate that the exed phenotype may either be a position effect on a distal gene caused by the c(6H) breakpoint or the result of composite effects of nullizygosity of multiple genes in the deletion homozygotes.