title: Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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 mug/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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medizinische Klinik und Poliklinik II, Universitätsklinikum Leipzig, Leipzig, Germany. lena.selig@medizin.uni-leipzig.de <lena.selig@medizin.uni-leipzig.de>
authors.forename: Lena
authors.initials: L
authors.lastname: Selig
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sack
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gaiser
authors.forename: Günter
authors.initials: G
authors.lastname: Klöppel
authors.forename: Vuk
authors.initials: V
authors.lastname: Savkovic
authors.forename: Joachim
authors.initials: J
authors.lastname: Mössner
authors.forename: Volker
authors.initials: V
authors.lastname: Keim
authors.forename: Hans
authors.initials: H
authors.lastname: Bödeker
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D001120:Arginine; D002108:Ceruletide; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D006639:Histidine; D006801:Humans; D008049:Lipase / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010179:Pancreas / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors; D019076:Transgenes; D014357:Trypsin; D014362:Trypsinogen / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D006639:Histidine; D002108:Ceruletide; D014362:Trypsinogen; D004247:DNA; D001120:Arginine; D008049:Lipase; D000681:Amylases; C489303:PRSS1 protein, human; D014357:Trypsin