Construction method of mouse model simulating human acute pancreatitis

Abstract

The invention discloses a construction method of a mouse model simulating human acute pancreatitis. Targeting vector plasmids containing PRSS1 genes are constructed and transferred to mouse embryonic stem cells electrically, and the mouse embryonic cells carrying the recombinant PRSS1 genes are obtained; the mouse embryonic cells carrying the recombinant PRSS1 genes are micro-injected into albinistic mouse blastodermal cells, the blastodermal cells receiving injection are transplanted to the uteri of pseudo-pregnant maternal mice, and chimeric mice are obtained after transplanting; male chimeric mice with the chimerism higher than 25% and wild C57BL / 6J female mice are mated, the next generation of mice are bred, and mice carrying PRSS1 genes are screened. The phenotype of the model mouse is greatly identical to the pathogenetic process of human acute pancreatitis, and the specific animal model completely simulating human acute pancreatitis from gene to phenotype is obtained and can be further widely applied to researches on pathopoiesis, pathomechanism and the like of human PRSS1 as well as screening and gene therapy tests of medicines for treating pancreatitis and the like.

Description

Technical field: [0001] The invention belongs to the field of animal model construction, in particular to a method for constructing a mouse model of human acute pancreatitis. Background technique: [0002] Acute pancreatitis (AP) is a clinically common and potentially fatal acute abdomen. Although great progress has been made in the diagnosis and treatment of AP, the fatality rate is still about 10%, and the severe cases reach 50%. The most important reason is that the specific mechanism of AP initialization has not been fully understood, and there is no way to guide the development of new and more effective drugs for the treatment of pancreatitis. Over the past 20 years, a large number of studies based on animal models of experimental pancreatitis have found that premature activation of trypsinogen in acinar cells plays a key role in the initialization of AP. However, the specific mechanism of trypsingen activation and its role in the development of pancreatitis have not ...

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Problems solved by technology

The conclusions of the above two experiments are partly contradictory, and the reason is that the transgenic mice used are defective: the promoters used to express the target gene are all rat-derived elastase, not human-derived elastase, so from There are fundamental doubts about the credibility of the experimental results

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