Functional analysis of the non-HLA genes within major histocompatibility complex (MHC) region with the use of gene-targeted mice

使用基因靶向小鼠对主要组织相容性复合体 (MHC) 区域内的非 HLA 基因进行功能分析

• 批准号: 11557013
• 负责人: MATSUMOTO Mitsuru
• 金额: $ 8.32万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557013/
• 关键词: complex; Autoimmune disease; Disease susceptibility; Knockout mice; 主要組織適合複合体; 疾患感受性遺伝子; 生体防御機構; 炎症

Since the discovery of the relationship between the geno-types of major histocompatibility complex (MHC) and susceptibility to many diseases, including autoimmune diseases, functional analysis of the genes within MHC region has been considered to be one of the most important issues for the better understanding of the processes involved in the development of many diseases. In order to reveal the mechanisms underlying the relationship between major histocompatibility complex (MHC)-type and disease susceptibility, we have been working on the generation of mice in which immune-related genes within the MHC region are deleted (knockout mice) with the use of gene-targeting technology. In this study, we have especially focused on the analysis of two genes near the TNF/lymphotoxin locus, because this locus contains many genes relevant to the development of inflammation. For one gene, chimeric mice have been generated, and the targeting vector has been constructed for the other gene, We are now in the process of generation of knockout mice for these two genes, We believe that analysis of the phenotype of these mice will also lead to a clear understanding of the function of the genes relevant to the host defence mechanism.

自从主要组织相容性复合体(MHC)基因类型与包括自身免疫性疾病在内的许多疾病的易感性之间的关系被发现以来，MHC区域基因的功能分析一直被认为是更好地了解许多疾病发生发展过程中的重要问题之一。为了揭示主要组织相容性复合体(MHC)类型与疾病易感性之间的关系，我们一直在利用基因打靶技术对MHC区域内免疫相关基因缺失的小鼠(基因敲除小鼠)进行研究。在这项研究中，我们特别关注靠近肿瘤坏死因子/淋巴毒素基因座的两个基因的分析，因为该基因座包含许多与炎症发生有关的基因。对于一个基因，嵌合小鼠已经产生，另一个基因的靶向载体已经构建，我们现在正在生成这两个基因的敲除小鼠的过程中，我们相信对这些小鼠的表型分析也将有助于清楚地了解与宿主防御机制相关的基因的功能。

项目成果

松本 満: "リンパ組織の形成におけるリンホトキシンとTNFの役割:ノックアウトマウスを用いた研究から得られた知見を中心に"日本リンパ網内系学会会誌. 38. 31-41 (1999)

Mitsuru Matsumoto：“淋巴毒素和 TNF 在淋巴组织形成中的作用：重点关注使用基因敲除小鼠的研究结果”日本淋巴网状系统学会杂志 38. 31-41 (1999)。

Nakano H.et al.: "Targeted disruption of Traf5 gene causes defects in CD40,-and CD27-mediated lymphocyte activation"Proc.Natl.Acad.Sci.USA.. 96. 9803-9808 (1999)

Nakano H.等人：“Traf5 基因的靶向破坏导致 CD40 和 CD27 介导的淋巴细胞激活缺陷”Proc.Natl.Acad.Sci.USA.. 96. 9803-9808 (1999)

Matsumoto,M.: "Role of TNF ligand and receptor family in the lymphoid organogenesis defined by gene targeting."J.Med.Invest.. 46. 141-150 (1999)

Matsumoto,M.：“TNF 配体和受体家族在基因靶向定义的淋巴器官发生中的作用。”J.Med.Invest.. 46. 141-150 (1999)

松本 満: "ノックアウトマウスを用いたMHC領域内non-HLA遺伝子機能の解析"生化学. 71. 323-332 (1999)

Mitsuru Matsumoto：“使用基因敲除小鼠分析 MHC 区域的非 HLA 基因功能”《生物化学》71. 323-332 (1999)。

Matsumoto, M., et al.: "Involvement of distinct cellular compartments in the abnorinal lymphoid organogenesis in lymphotoxin-α-deficient mice and alymphoplasia (aly) mice defined by the chimeric analysis"Journal of Immunology. 163. 1584-1591 (1999)

Matsumoto, M.等人：“通过嵌合分析定义淋巴毒素-α缺陷型小鼠和淋巴发育不全（aly）小鼠中不同细胞区室参与异常淋巴器官发生”《免疫学杂志》163。1584-1591（1999）。 ）