Flister Michael J, Joshi Amit, Bergom Carmen, Rui Hallgeir
Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Methods Mol Biol. 2019;2018:249-267. doi: 10.1007/978-1-4939-9581-3_12.
For nearly a century, the rat has served as a key model for studying the pathophysiology and genetic risk modifiers of breast cancer. Rat mammary tumors that initiate after exposure to carcinogens or estrogens closely resemble the etiological, histopathological, and genomic features of human breast cancer. Recent developments in genome-editing techniques in the rat have also enabled the development of sophisticated models for identifying the genetic modifiers of the nonmalignant tumor microenvironment that contribute to the formation, progression, and outcome of breast cancer. In this protocol review, we discuss the current methodologies for the three genetic mapping techniques in the rat that are widely used for identifying and testing the heritable genetic modifiers of breast cancer.
近一个世纪以来,大鼠一直是研究乳腺癌病理生理学和遗传风险修饰因子的关键模型。暴露于致癌物或雌激素后引发的大鼠乳腺肿瘤与人类乳腺癌的病因、组织病理学和基因组特征极为相似。大鼠基因组编辑技术的最新进展也推动了复杂模型的开发,用于识别对乳腺癌的形成、进展和转归有影响的非恶性肿瘤微环境的遗传修饰因子。在本方案综述中,我们讨论了大鼠中三种广泛用于识别和测试乳腺癌可遗传遗传修饰因子的遗传定位技术的当前方法。