Rescue of a lethal T/t locus genotype by chimaerism with normal embryos

Abstract

THE mutation T^Hp at the T/t locus in the mouse is unique among mammalian genes because it has a sharply defined maternal effect. Like other known T/t locus dominant mutations, T^Hp yields a short-tailed phenotype in heterozygotes of both sexes. However, T^Hp/+ females when mated with wild type fail to give birth to short–tailed progeny; examination of embryos shows that heterozygous embryos die late in gestation with seemingly minor defects such as spina bifida and polydactyly^1–3. The precise reason for death has not been determined, but must depend on some defect intrinsic to the egg, because T^Hp/+ females successfully carry to term heterozygous embryos whose T^Hp gene is paternally derived. I report here that lethal T^Hp/+ maternal heterozygotes are readily rescued if they are aggregated with normal embryos, but that the germ cell defect persists, because the chimaeras fail, if female, to transmit T^Hp to viable offspring.