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

本研究的目的是明确唇腭裂易感A/J系小鼠发生唇腭裂的原因。A/J小鼠的CL/P发病率明显高于其他品系小鼠，并可世代遗传。因此，我们分别从遗传因素和母体环境因素两方面研究了CL/P的发病原因，并将CL/P抗性小鼠与CL/P易感小鼠进行了杂交。然后观察子宫内的胚胎，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易感小鼠的胎盘数量较少，而CL/P抗性小鼠的胎盘数量较多。此外，在CL/P易感小鼠子宫内饲养的胚胎中，死胎和吸收率较高。很明显，在CL/P易感小鼠的子宫中培养胚胎比CL/P耐药小鼠更困难。然而，由于没有CL/P易感小鼠子宫内产生CL/P的F1胚胎，这表明母体环境因素是导致CL/P的原因。此外，通过将CL/P易感小鼠的受精卵移植到CL/P抗性小鼠子宫内，我们观察到CL/P的发生。结果，CL/P易感小鼠的胚胎在CL/P抗性小鼠子宫内产生CL/P。为了从实验上观察遗传因素，我们将CL/P易感小鼠的遗传基因导入CL/P耐药小鼠中，以提高遗传率，并观察发病率的变化。因此，随着CL/P易感小鼠遗传比例的增加，发病率也随之升高。这一结果表明，CL/P基因从CL/P易感小鼠传递到CL/P抗性小鼠。同时，该小鼠作为新建立的CL/P模型小鼠，CCC符合国际标准。

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.