title: Autoimmune disorder phenotypes in Hvcn1-deficient mice.
abstract: H(v) channels (voltage-gated proton channels) are expressed in blood cells, microglia and some types of epithelial cells. In neutrophils H(v) channels regulate the production of reactive oxygen species through regulation of membrane potential and intracellular pH. H(v) channels have also been suggested to play a role in sperm physiology in the human. However, the functions of the Hv channel at the whole-body level are not fully understood. In the present paper we show that Hvcn1 (voltage-gated hydrogen channel 1)-knockout mice show splenomegaly, autoantibodies and nephritis, that are reminiscent of human autoimmune diseases phenotypes. The number of activated T-cells was larger in Hvcn1-deficient mice than in the wild-type mice. Upon viral infection this was remarkably enhanced in Hvcn1-deficient mice. The production of superoxide anion in T-cells upon stimulation with PMA was significantly attenuated in the Hvcn1-deficient mice. These results suggest that H(v) channels regulate T-cell homoeostasis in vivo.
authors.affiliation: Laboratory of Integrative Physiology, Department of Physiology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Sasaki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tojo
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Okochi
authors.forename: Nana
authors.initials: N
authors.lastname: Miyawaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kamimura
authors.forename: Akihito
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Murakami
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okamura
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D010641:Phenotype; D017494:Proton Pumps / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D017494:Proton Pumps; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D013481:Superoxides