The Sp4H deletion may contain a new locus essential for postimplantation development.

Abstract Sp 4H is a semi-dominant mutation that maps to mouse chromosome 1. Heterozygous mice exhibit white spotting of the belly, whereas the fate of the homozygous embryos is unknown. We have previously shown that the entire coding region of the Pax3 gene is deleted in the Sp 4H mutant. In this study, we have analyzed the fate of the Sp 4H homozygous embryos. No Sp 4H homozygotes were detected by Southern blot or PCR analysis in 82 E9–E13-day embryos. We have also documented a significant increase in the number of resorption sites in Sp 4H heterozygous matings compared to control litters. Sections of the resorption sites (moles) suggest that postimplantation development is arrested prior to gastrulation. We have mapped the extent of the deletion to a maximum of 1.53 ± 0.6 cM using markers flanking the Pax3 locus. Four anonymous markers, D1Mit215, D1Mit253, D1Mit332, and D1McG156, have been shown to be deleted in the Sp 4H mutation. Further nondeleted markers have been used to extend the linkage map of this region. A total of 22 loci were analyzed in a Splotch intraspecific backcross. Using these data and deletion mapping data, we predict the following order of markers: ( D1Mit46, Vil )–( D1Mit79 )–( D1Mit132, D1McG153 )–( D1Mit332 )–( D1-McG156, D1Mit253, D1Mit215, Pax3 )–( D1Mit134 )–( D1Mit8, D1Mit9, D1Mit44, D1Ler3, D1Mit183 )–( D1Mit53, D1Mit82, D1Mit182 )–( Bcl2 ). As the deletion is large enough to include other genes, and it seems that deletion of Pax3 is not likely to account for the early death of the embryos, we suggest that another developmentally important gene may be deleted in the Sp 4H mouse mutant and that this may be responsible for the early death of the homozygous mutant embryos.