Development of disease model pigs suitable for diabetic complications research

开发适合糖尿病并发症研究的疾病模型猪

• 批准号: 23500505
• 负责人: NAGASHIMA Hiroshi
• 金额: $ 3.33万
• 依托单位: Meiji University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23500505/
• 关键词: ブタ; 遺伝子組換え動物; 病態モデル動物; 糖尿病; 合併症; 糖尿病腎症; 糖尿病網膜症

This study aimed at identifying the characteristics of transgenic(tg) pigs as a research model for diabetes and its complications. Tg pigs carrying a mutant gene, human HNF-1alpha(P291fsinsC), responsible for maturity-onset diabetes of the young type 3, were obtained by in vitro fertilization using the cryopreserved sperm from tg founder. The tg pigs maintained a high blood glucose level(>200mg/dl). The oral glucose tolerance test showed that the recovery of the blood sugar levels of the pigs was significantly delayed compared with non-tg pigs. The hypoplasia of the islets of Langerhans was confirmed by the histopathological image of the tg pigs' pancreas. The histopathological image of the tg pigs' kidney showed a nodular lesion typical of diabetic nephropathy in humans. Also, retinal hemorrhages and cotton-wool spots were confirmed in the tg pigs. These data demonstrate that the tg pigs is a promising model for research into diabetets and its complications.

本研究旨在鉴定转基因（tg）猪作为糖尿病及其并发症研究模型的特性。转基因猪携带的突变基因，人HNF-1 α（P291 fsinsC），负责成熟型糖尿病的年轻3型，获得体外受精使用冷冻保存的精子从tg创始人。tg猪维持高血糖水平（> 200 mg/dl）。口服葡萄糖耐量试验表明，与非转基因猪相比，转基因猪血糖水平的恢复明显延迟。通过tg猪胰腺的组织病理学图像证实胰岛发育不全。tg猪肾脏的组织病理学图像显示了人类糖尿病肾病的典型结节性病变。此外，在tg猪中证实了视网膜破裂和棉絮斑。这些数据表明，转基因猪是研究糖尿病及其并发症的一个很有前途的模型。

项目成果

The Minipig in Biomedical Research. Chapter 28, Creation and Conservation of Genetically Modified Pigs: Applications to Genetic Disease Model and Xenotransplantation

生物医学研究中的迷你猪。

• 发表时间: 2011
• 作者: Hiroshi Nagashima;Hitomi Matsunari;Kazuhiro Umeyama
• 通讯作者: Kazuhiro Umeyama

Diabetic retinopathy in transgenic pigs with induced diabetes mellitus

诱发糖尿病的转基因猪的糖尿病视网膜病变

• 发表时间: 2014
• 作者: Masami Nakajima;Akiko Ishimori;Kazuhiro Umeyama;Hiroshi Nagashima
• 通讯作者: Hiroshi Nagashima

糖尿病発症遺伝子改変ブタによるNonalcoholic fatty liver disease(NAFLD)病変の作出

转基因糖尿病猪产生非酒精性脂肪肝病（NAFLD）病变

• 发表时间: 2012
• 作者: 梅山一大;渡邊將人;本田香澄;竹内靖浩;中野和明;松成ひとみ;横尾隆;長嶋比呂志
• 通讯作者: 長嶋比呂志

糖尿病発症遺伝子改変ブタによる結節性病変を有した腎病変の作出

在转基因糖尿病猪中产生带有结节性病变的肾脏病变

• 发表时间: 2011
• 作者: 梅山一大;渡邊将人;松成ひとみ;他6名
• 通讯作者: 他6名

DIFFUSE GLOMERULAR NODULAR LESIONS IN DIABETIC PIGS CARRYING A DOMINANT-NEGATIVE MUTANT HEPATOCYTE NUCLEAR FACTOR ONE-ALPHA, AN INHERITANT DIABETIC GENE IN HUMANS

携带显性阴性突变肝细胞核因子 ONE-α（人类遗传性糖尿病基因）的糖尿病猪的弥漫性肾小球结节性病变

• 发表时间: 2014
• 作者: Satoshi Hara;Kazuhiro Umeyama;Takashi Yokoo;Hiroshi Nagashima;Michio Nagata
• 通讯作者: Michio Nagata