Mapping of genes that control the antibody response to human factor IX in mice.

Abstract:

: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 A/J and C57BL/6J mice and observed highly significant linkage (logarithmic odds [LOD] scores approximately 4.8) for the polymorphic D17Mit62 marker that is 1 centimorgan ( approximately 300 000 base pair [bp]) from the mouse major histocompatibility complex (MHC) locus (H-2). Experiments in mice with chimeric MHC genes indicated that class IaK or class II H-2 (or both) genes were critical, but other genes contributed to the antibody response. Polymorphic markers from 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 approximately 2.3-2.6) 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.

journal_name

Blood

journal_title

Blood

authors

Lozier JN,Tayebi N,Zhang P

doi

10.1182/blood-2004-03-1126

subject

Has Abstract

pub_date

2005-02-01 00:00:00

pages

1029-35

issue

3

eissn

0006-4971

issn

1528-0020

pii

2004-03-1126

journal_volume

105

pub_type

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