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Science 26 July 2002:
Vol. 297. no. 5581, pp. 620 - 623
DOI: 10.1126/science.1072810
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Reports

Identification of Bphs, an Autoimmune Disease Locus, as Histamine Receptor H1

Runlin Z. Ma,12 Jianfeng Gao,3 Nathan D. Meeker,2 Parley D. Fillmore,2 Kenneth S. K. Tung,4 Takeshi Watanabe,5 James F. Zachary,2 Halina Offner,6 Elizabeth P. Blankenhorn,7 Cory Teuscher3*

Bphs controls Bordetella pertussis toxin (PTX)-induced vasoactive amine sensitization elicited by histamine (VAASH) and has an established role in autoimmunity. We report that congenic mapping links Bphs to the histamine H1 receptor gene (Hrh1/H1R) and that H1R differs at three amino acid residues in VAASH-susceptible and -resistant mice. Hrh1-/- mice are protected from VAASH, which can be restored by genetic complementation with a susceptible Bphs/Hrh1 allele, and experimental allergic encephalomyelitis and autoimmune orchitis due to immune deviation. Thus, natural alleles of Hrh1 control both the autoimmune T cell and vascular responses regulated by histamine after PTX sensitization.

1 Laboratory Animal Center, Institute of Genetics, Chinese Academy of Sciences, Beijing, China 100101.
2 Department of Veterinary Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802-6178, USA.
3 Department of Medicine, University of Vermont, Burlington, VT 05405-0068, USA.
4 Department of Pathology, University of Virginia, Charlottesville, VA 22908-0001, USA.
5 Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
6 Department of Neurology, Oregon Health and Science University and Neuroimmunology Research, Veterans Affairs Medical Center, Portland, OR 97201-3098, USA.
7 Department of Microbiology and Immunology, MCP Hahnemann University, Philadelphia, PA 19129-1129, USA.
*   To whom correspondence should be addressed. E-mail: cteusche{at}zoo.uvm.edu

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