Development of new cleft lip and/or palate mouse using genetic englnnering - Study on fertility of reproduction cell and hereditary system -

利用基因工程培育新型唇裂和/或腭裂小鼠 - 生殖细胞生育能力和遗传系统的研究 -

• 批准号: 10557194
• 负责人: NATSUME Nagato
• 金额: $ 3.01万
• 依托单位: Aichi-Gakuin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10557194/
• 关键词: genetic engineering; cleft lip; cleft palate; A; J mouse; reprodctive function; CCC mouse; 生殖細胞

The purpose of this study is to make clear the cause of cleft lip and/or palate (CL/P) occurring in CL/P-prone A/J strain mouse. Incidence of CL/P in A/J mice obviously higher than in other strains and they inherit this characteristic for generations. Therefore, we studied about the causes of CL/P from genetic factor and maternal environmental factor respectively.We crossbred CL/P-resistant mice and CL/P-prone mice. Then observing embryos in the uteri, we studied about genetic and environmental factors. As a result, the number of placenta in CL/P-prone mice was low and that m CL/P-resistant mice was high regardless embryo's gene type. Also the rate of stillbirth and absorption was higher among embryos raised in the uteri of CL/P-prone mice. It was made clear that raising embryos in the uteri of CL/P-prone mice was more difficult than in CL/P-resistant mice. However, as there were no F1 embryos with CL/P raised in the uteri of CL/P-prone mice, it was suggested that maternal environmental factors were the cause of CL/P.Furthermore, by transplanting fertilized ova of CL/P-prone mice to uteri of CL/P-resistant mice, we observed the occurring of CL/P. As a result, CL/P occurred in embryos of CL/P-prone mice raised in the uteri of CL/P-resistant mice. This result suggested that genetic factor was the cause of CL/P rather than the environmental factor.In order to observe genetic factor experimentally, we put inherited gene of CL/P-prone mice into CL/P-resistant mice for generations to raise genetic ratio and observed the change of incidence. As a result, as genetic ratio of CL/P-prone mice raised, incidence raised. This result suggests that CL/P gene is transmitted to CL/P-resistant mice from CL/P-prone mice. At the same time, this mouse was admitted as a newly established CL/P model mouse, CCC to meet international standard.

本研究旨在阐明唇腭裂(CL/P)倾向于A/J品系小鼠发生唇腭裂的原因。A/J小鼠CL/P的发生率明显高于其他品系，并代代相传。因此，我们分别从遗传因素和母体环境因素两个方面对CL/P的病因进行了研究。然后观察子宫内胚胎，研究遗传和环境因素。结果表明，无论胚胎的基因类型如何，CL/P易感小鼠的胎盘数目较少，而mCL/P耐药小鼠的胎盘数目较高。CL/P倾向小鼠子宫内饲养的胚胎的死胎率和吸收率也较高。研究表明，在CL/P易感小鼠的子宫中饲养胚胎比在CL/P抗性小鼠中更难。然而，由于CL/P易感小鼠子宫内未出现CL/P的F1胚胎，提示母体环境因素是CL/P的发生原因。此外，将CL/P易感小鼠受精卵移植到CL/P耐药小鼠的子宫中，观察到CL/P的发生，结果CL/P易感小鼠在CL/P耐药小鼠子宫饲养的胚胎中出现CL/P。为了从实验上观察遗传因素对CL/P易感小鼠的影响，我们将CL/P易感小鼠的遗传基因植入CL/P耐药小鼠体内，以提高遗传率，并观察发病率的变化。结果表明，CL/P易感小鼠遗传比例越高，发病率越高。这一结果表明，CL/P基因从CL/P倾向的小鼠传递到CL/P耐药小鼠。同时，该小鼠被接纳为新建立的CL/P模型小鼠，符合国际标准。

项目成果

Nagato Natsume, Hiroo Furukawa, Teruyuki Niimi, Yoshinari Tanaka, Tetsuro Toyoda, Kazuo Kogure: "Pulmonary stenosis, ventricular septal defect and membrane defect in a beagle with cleft lip and palate."Aichi-Gakuin Dental Science. 14. 27-30 (2001)

Nagato Natsume、Hiroo Furukawa、Teruyuki Niimi、Yoshinari Tanaka、Tetsuro Toyoda、Kazuo Kogure：“唇腭裂小猎犬的肺动脉狭窄、心室间隔缺损和膜缺损。”爱知学院牙科科学。

Kaoru Yoshida, Nagato Natsume, Tsuyoshi Kawai, Hisahide Takahashi, Shizuko Nagao, Masao Kasahara, Yutaka Tsutsumi: "Development of cinnamon-colored CL/FR mouse, a new congenic strain for experimental Investigation of cleft lip with or without cleft palate

Kaoru Yoshida、Nagato Natsume、Tsuyoshi Kawai、Hisahide Takahashi、Shizuko Nagao、Masao Kasahara、Yutaka Tsutsumi：“肉桂色 CL/FR 小鼠的开发，这是一种新的同系品系，用于实验研究有或没有腭裂的唇裂

Nagato Natsume: "Pulmonary stenosis, ventricular septal defect and membrane defect in a beagle with cleft lip and palate"Aichi-Gakuin Dental Science. 14. 27-30 (2001)

长门夏目：“唇腭裂比格犬的肺动脉狭窄、室间隔缺损和膜缺损”爱知学院牙科科学。

Kaoru Yoshida: "Development of cinnamon-colored CL/FR mouse, a new congenic strain for experimental investigation of cleft lip with or without cleft palate"Aichi-Gakuin Dental Science. 14. 31-42 (2001)

吉田薰：“肉桂色 CL/FR 小鼠的开发，一种新的同源品系，用于实验研究有或没有腭裂的唇裂”爱知学院牙科科学。