The establishment of an in vivo system estimating the significance of a responsible gene for murine polygenic dianase model by using ES lines derived thorn the disease model

利用ES系衍生的刺疾病模型建立体内系统，评估鼠多基因双酶模型中负责基因的重要性

• 批准号: 18390126
• 负责人: NISHIMURA Hiroyuki
• 金额: $ 10.07万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390126/
• 关键词: gene; immunology

In polygenic disorders, the identification of a responsible gene is not only difficult but experimental systems to demonstrate the significance of the candidate gene in vivo has not yet been well established. In this report, we tried to identify a responsible gene with a polymorphism and to establish ES lines from polygenic mouse disease model to generate a mouse with the genes of normal alleles. To achieve this goal, two models were utilized: autoimmune dermatitis in MRL lpr mice and autoimmune diseases after thymectomized BALB/c but not C57BL/6 mice.1) Autoimmune dermatitis in MRL lpr miceWe paid attention to the different frequency of autoimmune dermatitis between MRL lpr (FAS receptor deficient) and MRL gld (its ligand deficiency) mice. Genes from C3H mice as MRL gld mice were generated were hypothesized to be responsible for the frequency. The region of C3H mice in MRL gld mice was determined between 38.1 and 102 cM in mouse chromosome 1. Because of the region, it was found that MRL gld mice should be backcrossed more generations to discover' responsible genes. On the other hand, ES cell lines were generated from MRL lpr mice. These cells expressed differential markers consistent with undifferentiated state and retained capability of generating chimeric mice after blastcyst injection but not of differentiating into germ cells.2) Autoimmune diseases in thymectomized BALB/c miceTo identify a responsible gene for different frequency of autoimmune diseases between thymectomized BALB/c and C57BL/6 mice, regulator genes for regulatory T cells were hypothesized to be involved. We found a gene with polymorphism in mouse chromosome 2 and generated a congenic BALB/c mice with the gene of C57BL/c mice and a congenic C57BL/c mice with the gene of BALB/c mice. These mice were expanded in number to examine the significance of the gene in the different frequency of autoimmune diseases.

在多基因疾病中，负责任基因的鉴定不仅很困难，而且实验系统证明体内候选基因的重要性尚未得到很好的确定。在本报告中，我们试图确定具有多态性的负责任基因，并从多基因小鼠疾病模型中建立ES线，以产生与正常等位基因基因的小鼠。为了实现这一目标，使用了两种模型：MRL LPR小鼠中的自身免疫性皮炎和胸膜切除术后的自身免疫性疾病，而不是C57BL/6小鼠。1）自身免疫性皮肤频率在MRL LPR的频率不同的频率和MRM MRM MRL LPR（Fas）（Fas）的不同频率（Fas）（Fas）（Fas）（Fas）（Fas）（Fas）（Fas）（Fas）和缺乏）小鼠。假设产生来自C3H小鼠作为MRL GLD小鼠的基因是频率的原因。 MRL GLD小鼠中C3H小鼠的区域在小鼠1中的38.1至102 cm之间确定。由于该区域，发现MRL GLD小鼠应反呼间更多世代，以发现“负责任的基因。另一方面，ES细胞系是由MRL LPR小鼠产生的。这些细胞表达了与未分化状态一致的差异标记，并保留了在爆炸注射后产生嵌合小鼠的能力，但不能区分生殖细胞。2）2）自身免疫性基因的自身免疫性疾病在不同频率的自身免疫性疾病中，胸膜疾病的胸膜疾病的基因和C57BL/C MICETO鉴定出胸膜疾病的基因和C57BL/C57BL/C57BL/C57BL/C57BL/COLL BAL BALB/CISTOM/C57BL/C57BL/C5。假设参与。我们在小鼠2中发现了一个具有多态性的基因，并用C57BL/C小鼠的基因产生了一个先天性的BALB/C小鼠，以及带有BALB/C小鼠基因的先天性C57BL/C小鼠。这些小鼠的数量扩大，以检查基因在自身免疫性疾病的不同频率下的重要性。

项目成果

Involvement of a tissue-specific antibody in skin disorders of murine systemic lupus erythematosus and autoinflammatory diseases

组织特异性抗体参与小鼠系统性红斑狼疮皮肤病和自身炎症性疾病

• 发表时间: 2006
• 期刊: Proc Natl Acad Sci U S A. 103
• 作者: Nishimura H;Strominger JL
• 通讯作者: Strominger JL

Involvement of a tissue-specific antibody in skin disorders of murine systemic lupus erythematosus and autoinflammatory diseases.

组织特异性抗体参与小鼠系统性红斑狼疮皮肤病和自身炎症性疾病。

• 发表时间: 2006
• 期刊: Proc Natl Acad Sci USA. : 103
• 作者: Nishimura H;Strominger JL
• 通讯作者: Strominger JL