Prevention of type 1 diabetes mellitus by the regulation of pancreas-specific retrovirus expression using the transplacental gene transfer method.

使用经胎盘基因转移方法调节胰腺特异性逆转录病毒表达来预防 1 型糖尿病。

• 批准号: 08457265
• 负责人: NAKAJIMA Hiromu
• 金额: $ 3.2万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457265/
• 关键词: type 1 diabetes mellitus; retrovirus; positional cloning; disease susceptible gene; viral infection; pancreas beta-cell destruction; NOD mouse; gene delivery method; 組織適合抗原遺伝子

The non-obese diabetic (NOD) mouse develop type I diabetes mellitus characterized by a massive lymphocytic infiltration into the pancreatic islets. A viral role has been suggested in the pathogenesis of this type of diabetes mellitus. We report here the cloning of retrovirus cDNA whose expression was considered to be specific to the pancreas of the NOD mouse. The provirus differs in sequence from all other published type C retrovirsues. The virus has a relatively well conserved gag region, and a truncated pol region with a large deletion. Almost all env region were deleted, and a trace of the sequence motif was included 3'to the pol region. These structural features are characteristic of replication defective viruses. Viral mRNA expression level was highest in 4-week-old NOD mice. The onset of insulitis also occurs from 4 weeks of age in the NOD mouse, thus suggesting a role for the virus in the pathogenesis of diabetes in this animal model.

非肥胖糖尿病 (NOD) 小鼠患上 I 型糖尿病，其特征是大量淋巴细胞浸润胰岛。已表明病毒在此类糖尿病的发病机制中发挥作用。我们在这里报道了逆转录病毒 cDNA 的克隆，其表达被认为是 NOD 小鼠胰腺特异的。原病毒在序列上与所有其他已发表的 C 型逆转录病毒不同。该病毒具有相对保守的gag区域和具有大缺失的截短pol区域。几乎所有的 env 区域都被删除，并且 pol 区域的 3' 端包含了一丝序列基序。这些结构特征是复制缺陷病毒的特征。 4周龄NOD小鼠的病毒mRNA表达水平最高。 NOD 小鼠也从 4 周龄开始出现胰岛素炎，这表明该病毒在该动物模型糖尿病的发病机制中发挥了作用。

项目成果

H.Nakajima, et al.: "Hepatocyle unclear factor-4α gene mutations in Japanese non-insulin dependent diabetes mellitus(NIDDM) patients." Res.Commun.Mol.Pathol.Pharmacol.94(3). 327-330 (1996)

H. Nakajima 等人：“日本非胰岛素依赖型糖尿病 (NIDDM) 患者的肝细胞因子 4α 基因突变。Res.Commun.Mol.Pathol.Pharmacol.94(3) (1996)。 ）

H.Iwahashi, T, H.Nakajima, et al.: "Cytokine-induced apoptotic cell death in a mouse pancreatic beta cell line:inhibition by Bcl-2." Diabetologia. 39(5). 530-536 (1996)

H.Iwahashi, T, H.Nakajima 等人：“小鼠胰腺 β 细胞系中细胞因子诱导的细胞凋亡：Bcl-2 的抑制。”

A.Imagawa,H.Nakajima,et al.: "High prevalence of antibodies to glutamic acid decarboxylase in comparision to islet cell antibodies in patients with long-standing insulin-dependent diabetes mellitus." Res.Commun.Mol.Pathol.Pharmacol.92(1). 43-52 (1996)

A.Imakawa、H.Nakajima 等人：“与长期胰岛素依赖型糖尿病患者的胰岛细胞抗体相比，谷氨酸脱羧酶抗体的患病率较高。”

A.Imagawa, H.Nakajima, et al.: "High prevalence of antibodies to glutamic acid decarboxylase in comparison to islet ccll antibodies in patients with long-standing insulin-depcndent diabetes mellitus." Res.Commun.Mol.Pathol.Pharmacol.92(1). 43-52 (1996)

A.Imakawa、H.Nakajima 等人：“在患有长期胰岛素依赖型糖尿病的患者中，与胰岛细胞抗体相比，谷氨酸脱羧酶抗体的患病率较高。”

K.Yamagata,H.Nakajima,et al.: "Dominant TCR α-chain clonotypes and interferon-γ are expressed in the pancreas of patients with recent-onset insulin-dependent diabetes mellitus." Diabetes Res.Clin.Practice. 34(9). 37-46 (1996)

K. Yamagata、H. Nakajima 等人：“新发胰岛素依赖型糖尿病患者的胰腺中表达了显性 TCR α 链克隆型和干扰素 γ”，34（糖尿病研究临床实践）。 9). 37-46 (1996)。