Yip1 domain family, member 6 (Yipf6) mutation induces spontaneous intestinal inflammation in mice
Yip1 domain family, member 6 (Yipf6) mutation induces spontaneous intestinal inflammation in mice
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DOI：
10.1073/pnas.1210366109
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发表时间：
2012-07-31
影响因子：
11.1
通讯作者：
Beutler, Bruce
中科院分区：
文献类型：
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作者：
Brandl, Katharina;Tomisato, Wataru;Beutler, Bruce
使用环境致敏的遗传筛选，我们确定了导致小鼠炎症性结肠炎的突变。X连锁Klein-Zschocher（KLZ）突变产生了Yipf 6的无效等位基因，Yipf 6是一个被认为调节酵母中囊泡运输的基因家族成员，但在哺乳动物中没有已知的功能。Yipf 6是一种与高尔基体区室相关的五跨膜蛋白。Klein-Zschocher突变体对葡聚糖硫酸钠（DSS）诱导的结肠炎极为敏感，在无特定病原体的饲养条件下，16个月后发生自发性回肠炎和结肠炎。电子显微镜，基因表达和免疫细胞化学分析提供的证据表明，受损的肠内稳态源于缺陷的形成和分泌的大分泌颗粒潘氏和杯状细胞。这些研究支持了Yipf 6在维持肠道内稳态中的组织和器官特异性功能，并暗示了作为疾病易感性位点的人类基因。
Using an environmentally sensitized genetic screen we identified mutations that cause inflammatory colitis in mice. The X-linked Klein-Zschocher (KLZ) mutation created a null allele of Yipf6, a member of a gene family believed to regulate vesicular transport in yeast, but without known functions in mammals. Yipf6 is a five transmembrane-spanning protein associated with Golgi compartments. Klein-Zschocher mutants were extremely sensitive to colitis induced by dextran sodium sulfate (DSS) and developed spontaneous ileitis and colitis after 16 mo of age in specific pathogen-free housing conditions. Electron microscopy, gene expression, and immunocytochemistry analyses provided evidence that impaired intestinal homeostasis stemmed from defective formation and secretion of large secretory granules from Paneth and goblet cells. These studies support a tissue- and organ-specific function for Yipf6 in the maintenance of intestinal homeostasis and implicate the orthologous human gene as a disease susceptibility locus.