Nature：炎症与癌症易感性

　　

生物通报道，Helen Diller Family Comprehensive癌症研究中心，加州大学医学院外科系，西班牙萨拉曼卡大学医学院，美国加州大学Lawrence Berkeley国家实验室，日本大学等研究机构的科学家构建了一个小鼠皮肤炎症与肿瘤易感性遗传图谱。

 

种系多态性影响生物机体和人类对某些特别疾病的易感性，这些特别的疾病比如说：癌症和炎症。研究者以Mus spretus种系的小鼠为研究对象，这一种属的小鼠是一种对肿瘤具有抵抗力的特殊小鼠，将这种小鼠与易感肿瘤小鼠Mus musculus进行杂交，并用图谱定位遗传变异表型寻找易患皮肤癌症的小鼠。通过遗传技术定位与炎症、血管发生、细胞复制和肿瘤易感的基因联系起来。

 

研究结果表明，有Lgr5标记的肠干细胞被鉴定为控制毛囊，维生素D受体（Vdr）调控因子，这些影响表皮功能正常与否，还与炎症和肿瘤易感性具有关联。

生物通 小茜

 

原文摘要：Genetic architecture of mouse skin inflammation and tumour susceptibility

【Abstract】

Germline polymorphisms in model organisms and humans influence susceptibility to complex trait diseases such as inflammation and cancer1, 2, 3, 4. Mice of the Mus spretus species are resistant to tumour development, and crosses between M. spretus and susceptible Mus musculus strains have been used to map locations of genetic variants that contribute to skin cancer susceptibility4, 5, 6. We have integrated germline polymorphisms with gene expression in normal skin from a M. musculus  M. spretus backcross to generate a network view of the gene expression architecture of mouse skin. Here we demonstrate how this approach identifies expression motifs that contribute to tissue organization and biological functions related to inflammation, haematopoiesis, cell cycle control and tumour susceptibility. Motifs associated with inflammation, epidermal barrier function and proliferation are differentially regulated in backcross mice susceptible or resistant to tumour development. The intestinal stem cell marker Lgr5 is identified as a candidate master regulator of the hair follicle, and the vitamin D receptor (Vdr) is linked to coordinated control of epidermal barrier function, inflammation and tumour susceptibility.