自建Tg.C57-ras V1.0小鼠模型与日本Tg.ras H2小鼠遗传学及其杂交1代生物学特性比较  被引量：1

作　　者：刘甦苏[1] 曹愿 杨艳伟[2] 王辰飞[1] 王三龙[2] 范昌发[1] LIU Susu;CAO Yuan;YANG Yanwei;WANG Cenfei;WANG Sanlon;FAN Changfa(Institute for Laboratory Animal Resources y National Institutes for Food and Drug Control,Beijing 102609,China;Beijing Key Laboratory for Safety Evaluation of Drugs,National Center for Safety Evaluation of Drugs National Institutes for Food and Drug Control,Beijing 100176,China)

机构地区：[1]中国食品药品检定研究院实验动物资源研究所,北京102629 [2]中国食品药品检定研究院国家药物安全评价监测中心,北京100176

出　　处：《实验动物科学》2021年第4期22-27,共6页Laboratory Animal Science

基　　金：中国食品药品检定研究院学科带头人培养基金(2019X2)。

摘　　要：目的比较自主建立的Tg.C57-ras小鼠与日本Tg.ras H2小鼠模型的遗传学及Tg.C57-ras转基因小鼠与BALB/c小鼠的杂交1代小鼠(简称CB6F1-NIFDC)与日本Tg.ras H2转基因小鼠模型杂交1代小鼠(简称CB6F1-CIEA)的生物学特性,为国内药物安全评价机构提供致癌性模型的多元化选择。方法对两种模型的遗传学及生物学特性进行比较,包括模型构建方法、转录水平、蛋白水平、生长曲线、血液生理数据等。结果遗传学特性:两种模型均采用转基因方法构建,转入c-Ha-ras基因序列无实质差异,拷贝数仅相差一个;两种模型的不同脏器在mRNA水平基因表达具有相似性;日本模型肺组织的蛋白水平稍高于自主建立模型,但无统计学差异。生物学特性:根据文献分析两种模型杂交1代的生长曲线有差异,但在致癌实验周期内两模型体质量差别不大;血液生理指标有部分差异。结论通过遗传学及生物学特性比较,自建模型可作为临床前药物致癌性评价的候选模型。Objective Compared the genetics of the independently established Tg.C57-ras mouse and Japanese Tg.ras H2 mouse model,and the biological characteristics of the first generation of hybrid mice between Tg.C57-ras transgenic mice and BALB/c mice(CB6 F1-NIFDC)and Japanese Tg.ras H2 transgenic mouse model(CB6 F1-CIEA),which provided theoretical support for applying self-established mouse model in new drug preclinical carcinogenicity evaluation.Method The genetic characteristics,biological characteristics and sensitivity to positive carcinogens of the 2 models and F1 models were analyzed.Result The 2 models was used to construct by the genetically modified method.Analysis of genetics features showed that c-Ha-ras gene fragment has no actual difference,and only 1 copy difference in the copy number.mRNA expression level shows that genes in different organs of the two models are similar.But although the lung tissue protein levels in the Japanese model is slightly higher than the independent model,it reached no statistical difference.According to literature review and analysis,the growth curves of the 2 models were different,but there was little difference in body weight during the carcinogenic experiment cycle.There are some differences in blood physiological and biochemical indexes,and these differences were estimated to be related to genetic background.Conclusion Due to the comparing the characteristic data from 2 aspects,it is suggested that Tg.C57-ras transgenic mice established by ourselves may be a promising candidate animal model for development of a rapid carcinogenicity testing system for preclinical safety evaluation of drugs.

关 键 词：Tg.C57-ras小鼠 Tg.ras H2小鼠 遗传学特性 生物学特性 药物安全评价 

分 类 号：Q95-33[生物学—动物学]