Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Lab Invest. 2010 May;90(5):654-64. doi: 10.1038/labinvest.2010.44. Epub 2010 Feb 15.
To analyze susceptibility to acute pancreatitis, five mouse strains including Japanese Fancy Mouse 1 (JF1), C57BL/6J, BALB/c, CBA/J, and C3H/HeJ were treated with either a cholecystokinin analog, cerulein, or a choline-deficient, ethionine-supplemented (CDE) diet. The severity of acute pancreatitis induced by cerulein was highest in C3H/HeJ and CBA/J, moderate in BALB/c, and mildest in C57BL/6J and JF1. Basal protein expression levels of the serine protease inhibitor, Kazal type 3 (Spink3) were higher in JF1 and C57BL/6J mice than those of the other three strains under normal feeding conditions. After treatment with cerulein, expression level of Spink3 increased remarkably in JF1 and mildly in C57BL/6J, BALB/c, CBA/J, and C3H/HeJ strains. Increased proteinase, serine, 1 (Prss1) protein expression accompanied by increased trypsin activity with cerulein treatment was observed in susceptible strains such as CBA/J and C3H/HeJ. Similar results were obtained with a CDE diet. In the 3 kb Spink3 promoter region, 92 or 8 nucleotide changes were found in JF1 or C3H vs C57BL/6J, respectively, whereas in the Prss1 promoter region 39 or 46 nucleotide changes were found in JF1 or C3H vs C57BL/6J, respectively. These results suggest that regulation of Prss1 and Spink3 expression is involved in the susceptibility to experimentally induced pancreatitis. The JF1 strain, which is derived from the Japanese wild mouse, will be useful to examine new mechanisms that may not be found in other laboratory mouse strains.
为了分析急性胰腺炎的易感性,五种小鼠品系,包括日本 fancy 小鼠 1 (JF1)、C57BL/6J、BALB/c、CBA/J 和 C3H/HeJ,分别用胆囊收缩素类似物、亮氨酸脑啡肽或胆碱缺乏、蛋氨酸补充(CDE)饮食处理。亮氨酸脑啡肽诱导的急性胰腺炎严重程度在 C3H/HeJ 和 CBA/J 中最高,在 BALB/c 中中等,在 C57BL/6J 和 JF1 中最低。在正常喂养条件下,JF1 和 C57BL/6J 小鼠的丝氨酸蛋白酶抑制剂,Kazal 型 3(Spink3)的基础蛋白表达水平高于其他三种品系。用亮氨酸脑啡肽处理后,Spink3 的表达水平在 JF1 和 C57BL/6J 中显著增加,在 BALB/c、CBA/J 和 C3H/HeJ 中轻度增加。在易感品系如 CBA/J 和 C3H/HeJ 中,用亮氨酸脑啡肽处理后观察到蛋白酶、丝氨酸、1(Prss1)蛋白表达增加,同时胰蛋白酶活性增加。用 CDE 饮食也得到了类似的结果。在 3kb Spink3 启动子区,JF1 或 C3H 与 C57BL/6J 相比分别发现 92 或 8 个核苷酸变化,而在 Prss1 启动子区,JF1 或 C3H 与 C57BL/6J 相比分别发现 39 或 46 个核苷酸变化。这些结果表明,Prss1 和 Spink3 表达的调节参与了实验性胰腺炎的易感性。JF1 品系源自日本野生鼠,将有助于研究可能在其他实验鼠品系中未发现的新机制。