NOVEL INHERITANCE OF THE MURINE SEVERE COMBINED ANEMIA AND THROMBOCYTOPENIA (SCAT) PHENOTYPE

The phenotype of the autosomal recessive mutation scat includes severe intermittent bleeding, depletion of platelets, and circulating anti-platelet antibodies. In this study, we have mapped the scat mutation to mouse chromosome 8 and shown that the immune component is a secondary consequence of the gene defect. Surprisingly, the phenotype of the scat/scat pups depends on the genotype of the mother. Maternal homozygosity prevents disease transmission; crosses between scat homozygotes produce few affected young, while the expected frequency is generated from normal (+/+) mice bearing scat/scat ovaries. The results suggest a novel method of maternal-fetal interaction that relies neither on transfer of maternal mitochondria nor on parental imprinting. We conclude that contribution from the maternal wild-type allele is required for expression of the scat phenotype in homozygotes.