The Splotch (Sp1H) and Splotch-delayed (Spd) alleles: differential phenotypic effects on neural crest and limb...

Homozygous mutants of the murine Splotch (Sp1H) and the Splotch-delayed (Spd) alleles show different phenotypes with respect to neural crest derivatives and their longevity. In this report, Sp1H/Sp1H, Spd/Spd and Sp1H/Spd mouse mutant embryos were examined histologically in serial sections on day 13.5 of gestation. All Spd/Spd and Sp1H/Spd embryos showed a similarly dramatic reduction of the muscle primordia in the limbs that had previously been observed in Sp1H homozygotes. The neural crest-derived spinal ganglia and Schwann cells showed major defects in Sp1H homozygotes and lesser defects in Spd homozygote, with Sp1H/Spd embryos being intermediary. Also, the neural crest-derived septum of the truncus arteriosus was formed in almost none of the Sp1H homozygotes, in roughly half of the Sp1H/Spd double heterozygotes and in all of the Spd homozygotes. Aortic conus malformations were observed in all mutants. The paternal origin of the Sp1H allele in the Sp1H/Spd embryos had no influence on the resulting phenotype. These observations demonstrate that the neural tube defect and the limb muscle defect are the common denominator of both the Splotch and the Splotch-delayed phenotype. The extent of the neural crest defects in the mutant compounds apparently depends on the Splotch alleles involved.