Identification of Two Major Loci Linked to Autoimmune Hemolytic Anemia in NZB Mice
نویسندگان
چکیده
Using a cohort of C57BL/6 (B6) x (NZB x B6)F1 backcross male mice bearing the Yaa (Y-linked autoimmune acceleration) mutation, we mapped and characterized the NZB-derived susceptibility loci predisposing to the development of autoimmune hemolytic anemia (AHA). Our analysis identified two major loci on NZB chromosome 7 and chromosome 1 linked with Coombs’ anti-erythrocyte autoantibody production, and their contributions were confirmed by the analysis of B6.Yaa mice congenic for each NZB-derived susceptibility interval. A newly identified Aia3 (autoimmune anemia 3) locus present on NZB chromosome 7 selectively regulated Coombs’ antibody responses, while the second locus, directly overlapping with Nba2 (NZB autoimmunity 2) on chromosome 1, promoted the development of AHA, likely as part of its effect on overall production of lupus autoantibodies. A higher incidence of Coombs’ antibody production in B6.Aia3 congenic mice than B6.Nba2 mice indicated a major role for Aia3 in AHA. Notably, lack of expansion of B1 cells in B6.Aia3 congenic mice argued against the involvement of this subset in AHA. Finally, our analysis of BC mice also demonstrated the presence of a B6-derived H2-linked locus on chromosome 17 that apparently regulated the production of Coombs’ antibodies as a result of its overall autoimmune promoting effect. For personal use only. on April 13, 2017. by guest www.bloodjournal.org From
منابع مشابه
Identification of 2 major loci linked to autoimmune hemolytic anemia in NZB mice.
Using a cohort of C57BL/6 (B6) x (NZB x B6)F1 backcross male mice bearing the Yaa (Y-linked autoimmune acceleration) mutation, we mapped and characterized the NZB-derived susceptibility loci predisposing to the development of autoimmune hemolytic anemia (AHA). Our analysis identified 2 major loci on NZB chromosome 7 and chromosome 1 linked with Coombs antierythrocyte autoantibody production, an...
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