自建 Tg. C57-ras V1. 0 小鼠模型与日本 Tg. rasH2小鼠遗传学及其杂交 1 代生物学特性比较

摘要:目的 比较自主建立的 Tg. C57-ras 小鼠与日本 Tg. rasH2 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. rasH2 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。

Similarities and Differences between the Self-established Tg. C57-ras V1. 0Transgenic Mice Model and Japanese Tg. rasH2 Mice Model

Abstract: Objective Compared the genetics of the independently established Tg. C57-ras mouse and JapaneseTg. rasH2 mouse model, and the biological characteristics of the first generation of hybrid mice between Tg. C57-ras transgenic mice and BALB / c mice ( CB6F1-NIFDC) and Japanese Tg. rasH2 transgenic mouse model ( CB6F1-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 slightlyhigher 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.