The phenotype of the autosomai 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 (+ I+) 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. introduction

In mice homozygous for the autosomal recessive mutation scat (severe combined anemia and thrombocytopenia)(Peters et al., 1990), episodic bleeding coincides with a cyclical platelet deficiency and results in pancytopenia and early death (mean survival time of 22 days). Marked spienomegaiy accompanies the bleeding crises. Histoiogicaiiy, the lymphatic nodules of the spleen are effaced by large mononuclear ceils of unknown origin and there are increased numbers of megakaryocytes. Homozygous scat/scat mice are severely affected at birth, but approximately 40% survive and enter a spontaneous remission period free of ail overt symptoms (petechiae and extreme pallor). During this remission period, which begins around day 16 and lasts an average of 11 days, the spleen size and histology and the peripheral erythrocyte, leukocyte, and platelet counts revert to normal or are markedly improved. A second crisis period ensues, and 90% of all scat/scat mice are dead by the age of 50 days. Notably, a small fraction (7.5%) of scat/scat mice enter an extended remission period and some can produce young.