| First Author | Ida A | Year | 1998 |
| Journal | Eur J Immunol | Volume | 28 |
| Issue | 9 | Pages | 2694-703 |
| PubMed ID | 9754557 | Mgi Jnum | J:49899 |
| Mgi Id | MGI:1289373 | Doi | 10.1002/(SICI)1521-4141(199809)28:09<2694::AID-IMMU2694>3.0.CO;2-# |
| Citation | Ida A, et al. (1998) Multigenic control of lupus-associated antiphospholipid syndrome in a model of (NZW x BXSB) F1 mice. Eur J Immunol 28(9):2694-703 |
| abstractText | 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. |
