In a subset of systemic lupus erythematosus (SLE) patients, antiphospholipid 
syndrome, characterized by occurrence of anti-cardiolipin (CL) antibodies, 
thrombocytopenia, thrombosis and recurrent intrauterine fetal death occurs. Male 
(NZW x BXSB)F1 mice, carrying the BXSB Yaa gene, serve as a model for 
SLE-associated antiphospholipid syndrome. Using microsatellite markers in the 
NZW x (NZW x BXSB)F1 backcross male progeny, we mapped BXSB alleles contributing 
to the generation of anti-CL antibodies, platelet-binding antibodies, 
thrombocytopenia and myocardial infarction. Generation of each disease character 
was controlled by two major independently segregating dominant alleles, i.e. 
those on chromosomes (Chr.) 4 and 17 for anti-CL antibodies, Chr. 8 and 17 for 
both anti-platelet antibodies and thrombocytopenia and, to our surprise, Chr. 7 
and 14 for myocardial infarction, and that a combination of the two alleles 
appeared to produce full expression of each character, as a complementary gene 
action. The alleles on Chr. 17 linked to the above three characters were all 
mapped in close proximity to the H-2 complex. Therefore, no single factor such 
as anti-CL antibodies can explain the pathogenesis of SLE-associated 
antiphospholipid syndrome. Rather, a combination of susceptibility alleles such 
as described here, along with additional modifying loci, i.e. BXSB Yaa and some 
from NZW, characterizes unique SLE features in male (NZW x BXSB) F1 mice. There 
are potentially important candidate genes which may be linked to the syndrome.