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.

自从发现主要组织相容性复合物（MHC）的Geno类型与对许多疾病（包括自身免疫性疾病）的易感性之间的关系之间存在关系，因此人们认为对MHC区域内基因的功能分析被认为是对许多疾病发展涉及过程的更好理解的最重要问题之一。为了揭示主要组织相容性复合物（MHC） - 类型和疾病易感性之间关系的机制，我们一直在研究MHC区域内免疫相关基因（基因敲除小鼠）中与基因靶向技术的使用。在这项研究中，我们特别关注对TNF/淋巴毒素基因座附近的两个基因的分析，因为该基因座包含许多与炎症发展有关的基因。对于一个基因，已经生成嵌合小鼠，并且已经为另一个基因构建了靶向载体，现在我们正在为这两个基因生成基因敲除小鼠的过程，我们相信对这些小鼠表型的分析也将导致对与宿主防御机制相关的基因功能的清晰了解。

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)。

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）。 ）

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)。

Matsushima,A. et al.: "Essential role of NF-κB-inducing kinase and iκB-kinase α in NF-κB activation through Iymphotoxin-β receptor, but hot through TNF receptor-1"Journal of Experimental Medicine. 193. 631-636 (2001)

Matsushima, A. 等人：“NF-κB 诱导激酶和 iκB 激酶 α 在通过淋巴毒素-β 受体激活 NF-κB 中的重要作用，但通过 TNF 受体-1 激活”实验医学杂志 193. 631。 -636 (2001)