Identification of Bphs, an autoimmune disease locus, as histamine receptor H1.
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.
Ma
Runlin Z
RZ
Laboratory Animal Center, Institute of Genetics, Chinese Academy of Sciences, Beijing, China 100101.
Gao
Jianfeng
J
Meeker
Nathan D
ND
Fillmore
Parley D
PD
Tung
Kenneth S K
KS
Watanabe
Takeshi
T
Zachary
James F
JF
Offner
Halina
H
Blankenhorn
Elizabeth P
EP
Teuscher
Cory
C
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000235:genetics / Q000276:immunology; D005816:Genetic Complementation Test; D020022:Genetic Predisposition to Disease; D006632:Histamine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D037342:Pertussis Toxin; D020641:Polymorphism, Single Nucleotide; D011969:Receptors, Histamine H1 / Q000737:chemistry / Q000235:genetics*; D015290:Second Messenger Systems; D013601:T-Lymphocytes / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000633:toxicity
D016207:Cytokines; D011969:Receptors, Histamine H1; D010566:Virulence Factors, Bordetella; D006632:Histamine; D037342:Pertussis Toxin