Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen.
Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen.
复制标题
表达R122H人阳离子胰蛋白酶原的转基因小鼠的表征。
DOI：
10.1186/1471-230x-6-30
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发表时间：
2006-10-27
影响因子：
2.4
通讯作者：
Boedeker, Hans
中科院分区：
文献类型：
--
作者：
Selig, Lena;Sack, Ulrich;Gaiser, Sebastian;Kloeppel, Guenter;Savkovic, Vuk;Moessner, Joachim;Keim, Volker;Boedeker, Hans
在遗传性胰腺炎患者中发现了阳离子胰蛋白酶原的R122 H突变。携带这种突变的转基因动物可以作为胰腺炎的遗传模型系统。使用大鼠弹性蛋白酶启动子的-205片段产生人R122 H阳离子胰蛋白酶原转基因小鼠。在DNA、胰腺mRNA和酶原颗粒裂解物中测定转基因的存在。监测血清淀粉酶、脂肪酶和细胞因子（MCP-1、IL-6）水平，并研究组织的组织学外观。通过每7小时注射50 μg/kg雨蛙肽诱导胰腺炎。每周重复两次，连续10周。在首次注射后24小时（n = 8）和48小时（n = 8）以及整个给药结束时（n = 7）处死动物。在基因组水平和胰腺mRNA中检测到转基因。在酶原颗粒裂解物中发现少量的相应蛋白质。R122 H小鼠显示胰脂肪酶升高，但在18个月内没有自发性胰腺炎的发生。诱导胰腺炎后，与对照组相比，R122 H小鼠的脂肪酶（24小时后）和淀粉酶（48小时后）水平较高。重复使用雨蛙肽治疗导致R122 H动物的胰腺炎稍微更严重。淀粉酶、脂肪酶和细胞因子水平与对照组相似。R122 H转基因小鼠未能发展为自发性胰腺炎，但反复激发的蛙皮素诱导的胰腺炎导致稍微更严重的胰腺炎。与对照相比，相当小的差异可能是由于小鼠胰腺中转基因的低表达。
The R122H mutation of the cationic trypsinogen was found in patients with hereditary pancreatitis. A transgenic animal carrying this mutation could be useful as a genetic model system of pancreatitis. Mice transgenic for the human R122H cationic trypsinogen were generated using the -205 fragment of the rat elastase promoter. The presence of the transgene was assayed in the DNA, in pancreatic mRNA and in zymogen granule lysates. Serum levels of amylase, lipase and cytokines (MCP-1, IL-6) were monitored and the histological appearance of the tissue was investigated. Pancreatitis was induced by 7 hourly injections of 50 μg/kg cerulein. The procedure was repeated twice weekly for 10 consecutive weeks. The animals were sacrificed 24 (n = 8) and 48 hours (n = 8) after the first injection and at the end of the whole treatment (n = 7). The transgene was detected at the genomic level and in pancreatic mRNA. The corresponding protein was found in low amounts in zymogen granule lysates. R122H mice showed elevated pancreatic lipase, but there was no spontaneous development of pancreatitis within 18 months. After induction of pancreatitis, levels of lipase (after 24 hours) and amylase (after 48 hours) were higher in R122H mice compared to controls. Repeated treatment with cerulein resulted in a slightly more severe pancreatitis in R122H animals. Amylase, lipase, and the cytokine levels were similar to controls. The R122H transgenic mouse failed to develop a spontaneous pancreatitis but a repeatedly provoked cerulein-induced pancreatitis led to a slightly more severe pancreatitis. The rather small difference in comparison to controls could be due to the low expression of the transgene in the mouse pancreas.