1995 Fiscal Year Final Research Report Summary
Production of Experimntal Model Mice for Studies of lmmunogical Diorders by Gene Targeting.
| Project/Area Number |
06557025
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
KIKUTANI Hitoshi lnst.Molec.& Cell.Biol., Osaka Univ., Assoc.Prof., 細胞生体工学センター, 助教授 (80161412)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Experimental model mouse / Knock-out mouse / Hemoral immune response / CD40 / CD23 / Autoimmune / Infection / Cell-mediated immune response |
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| Research Abstract |
CD40 is known to deliver an important costimulatory signal to B cells. CD23 is a low affinity receptor for IgE on lymphocytes. Both molecules have been suggested to play important roles in regulation of humoral and cell-mediated immune responses. To develop the experimental system and model mice for studying the immune system and immunological diseases, the mice deficient in CD40 or CD23 have been generated by gene targeting of embryonic stem cells. In CD40-deficient mice, Ig class switching and germinal center formation were severely impaired. The development of functional helper T cells was also affected in the absence of CD40. The CD40-deficient mice were susceptible to infection with the intracellular protozoan, Leishmania major because they failed to mount a T helper 1 response to parasites in the absence of CD40. By backcrossing the CD40-deficient into the type I diabetes model, NOD,we produced CD40-deficient NOD mice. CD40-deficient NOD never developed autoimmune insulitis and diabetes. These results demonstrate that CD40-deficient mice can be an ideal experimental model for infectious diseases as well as autoimmune diseases. In CD23-deficient mice, IgE antibody-mediated antigen focusing by antigen presenting cells was absent. CD23-deficient mice mounted higher levels of IgE responses when immunized with protein antigens, suggesting a possible role of CD23 in negative feedback in IgE production. Furthermore, experimental airway hyperresponsiveness is less severe in CD23-deficient mice than in wild-type littermates, indicating that CD23-deficient mice can be a experimental model to study the pathogenesis of asthma.
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[Publications] Fujiwara, H., H.Kikutani, S.Suematsu, T.Naka, K.Oshida, K.Yoshida, T.Tanaka, M.Suemura, N.Matsumoto, S.Kojima, T.Kishimoto, and N.Yoshida.: "The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice." Proc.Natl.Acad.Sci., USA. 91. 6835-6839 (1994)
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「研究成果報告書概要(欧文)」より
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[Publications] Fujiwara, H., H.Kikutani, S.Suematsu, T.Naka, K.Yoshida, T.Tanaka, M.Suemura, T.Kishimoto, and N.Yoshida.: "Functional characterization of Cd23 by targeted disruption of the mouse CD23 gene." Leucocyte Typing V "White Cell Differentiation Antigens" edt. by S.F.Schlossman, et al.Oxford Univ.Press.534-535 (1995)
Description
「研究成果報告書概要(欧文)」より
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