Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone New Zealand Black mice

New Zealand Black (NZB) mice spontaneously produce anti-erythrocyte autoant ibodies (AEA) in association with splenomegaly, thus serving as a model for autoimmune hemolytic anemia, Although these autoimmune traits are inherite d as a dominant fashion, expression in F-1 hybrids of NZB and most non-New Zealand strains is suppressed due to the contribution of wild-type modifyin g genes present in the latter strains. Using chromosomal microsatellite mar kers in the (C57BL/6 x NZB)F-1 x NZB backcross progeny, we mapped C57BL/6 m odifying loci for AEA production and splenomegaly, Generation of AEA was fo und to be down-regulated by a combined effect of two major independently se gregating dominant alleles--one linked to D7MIT30 on chromosome 7 and the o ther linked to D10MIT42 on chromosome 10, Splenomegaly was modified mainly by a single C57BL/6 allele linked to D4MIT58 on chromosome 4, Thus, the aut oimmune hemolytic anemia in the NZB strain is under multigenic control and a combined action of not only susceptibility but also modifying alleles wit h suppressive activities affects the outcome of disease features in the pro geny. There are potentially important candidate genes which may be linked t o the regulation of AEA and splenomegaly.