大鼠是一種用于研究人類生理和疾病的廣泛使用的動(dòng)物模型,,但功能基因組學(xué)和遺傳研究一直因基因定位工具有限而受阻。
現(xiàn)在,,應(yīng)其龍(音譯)及其同事建立了通過大鼠胚胎干(ES)細(xì)胞中的同源重組來進(jìn)行基因定位的方法,,并且首次培育出了p53基因被剔除的大鼠,它們適合對(duì)普遍存在的腫瘤抑制因子p53進(jìn)行生理研究和藥理研究,。(生物谷Bioon.com)
生物谷推薦英文摘要:
Nature doi:10.1038/nature09368
Production of p53 gene knockout rats by homologous recombination in embryonic stem cells
Chang Tong,Ping Li,Nancy L. Wu,Youzhen Yan& Qi-Long
The use of homologous recombination to modify genes in embryonic stem (ES) cells provides a powerful means to elucidate gene function and create disease models1. Application of this technology to engineer genes in rats has not previously been possible because of the absence of germline-competent ES cells in this species. We have recently established authentic rat ES cells2, 3. Here we report the generation of gene knockout rats using the ES-cell-based gene targeting technology. We designed a targeting vector to disrupt the tumour suppressor gene p53 (also known as Tp53) in rat ES cells by means of homologous recombination. p53 gene-targeted rat ES cells can be routinely generated. Furthermore, the p53 gene-targeted mutation in the rat ES-cell genome can transmit through the germ line via ES-cell rat chimaeras to create p53 gene knockout rats. The rat is the most widely used animal model in biological research4, 5, 6, 7. The establishment of gene targeting technology in rat ES cells, in combination with advances in genomics and the vast amount of research data on physiology and pharmacology in this species, now provide a powerful new platform for the study of human disease.