Mapping of genes that control the antibody response to human factor IX in mice
Mapping of genes that control the antibody response to human factor IX in mice
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DOI：
10.1182/blood-2004-03-1126
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发表时间：
2005-02-01
期刊：
影响因子：
20.3
通讯作者：
Zhang, P
中科院分区：
文献类型：
--
作者：
Lozier, JN;Tayebi, N;Zhang, P
We tested the hypothesis that the antibody response to human factor IX in mice is controlled by genetic factors, especially histocompatibility antigens. Seven inbred mouse strains were immunized against human factor IX by adenoviral gene transfer or serial injections of human factor IX protein. A/J mice had the highest antibody response and 2 C57 mouse strains had the lowest response. We used the adenovirus vector to immunize 26 recombinant inbred mouse strains (AXB and BXA) derived from AM and C57BL/6J mice and observed highly significant linkage (logarithmic odds [LOD] scores similar to4.8) for the polymorphic D17Mit62 marker that is 1 centimorgan (similar to300 000 base pair [bpl]) from the mouse major histocompatibility complex (MHC) locus (H-2). Experiments in mice with chimeric MHC genes indicated that class laK or class II H-2 (or both) genes were critical, but other genes contributed to the antibody response. Polymorphic markersfrom chromosomes 1 and 10 that are near important immunoregulatory genes such as interleukin 10 and the interferon-gamma gene show suggestive linkage (LOD scores of similar to2.3-2.6) to the factor IX antibody response. This study confirms the hypothesis that H-2 (and other) genes control factor IX antibody development in mice and suggests their potential importance for factor IX antibody development in humans with hemophilia B. (C) 2005 by The American Society of Hematology.
