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Modelling chronic pancreatitis as a complex genetic disease in mice
  1. Zsanett Jancsó,
  2. Alexandra Demcsák,
  3. Miklós Sahin-Tóth
  1. Department of Surgery, University of California Los Angeles, Los Angeles, California, USA
  1. Correspondence to Dr Miklós Sahin-Tóth, Department of Surgery, University of California Los Angeles, Los Angeles, CA 90095, USA; msahintoth{at}mednet.ucla.edu

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We read with great interest the recent articles by Wang et al,1 Génin et al,2 Sun et al,3 and Németh et al,4 in which the authors studied various genetic risk factors for chronic pancreatitis (CP). The ever increasing catalogue of risk genes and variants supports the long-held notion that CP is a complex genetic disorder. Thus, patients often carry multiple genetic alterations that interact in synergy and elicit disease onset and/or promote progression. To offer a conceptual framework for genetic risk in CP, we organised risk factors into mechanism-based schemes, which include the trypsin-dependent, misfolding-dependent and ductal pathways.5

More recently, novel mouse models harbouring human pancreatitis-associated mutations emerged, providing strong evidence for the pathogenic nature of these risk variants.3 6–10 All mouse models of genetic CP published to date carry a single genetic alteration and none models CP as a complex genetic disease. We set out to fill this knowledge gap by generating a novel strain carrying both the T7K24R trypsinogen mutant and the Ctrb1-del chymotrypsin deletion alleles. The T7K24R mice have the p.K24R mutation in mouse cationic trypsinogen (isoform T7), which is analogous to the human hereditary pancreatitis-associated p.K23R PRSS1 mutation.9 This mutation increases …

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Footnotes

  • Contributors Study concept and design: ZJ, MS-T. Experiments: ZJ, AD. Acquisition, analysis or interpretation of data: all authors. Drafting of the manuscript: MST, AD. Critical revision of the manuscript for important intellectual content: all authors. Obtained funding: MST, ZJ. Administrative, technical or material support: all authors. Study supervision: MST. Final approval of manuscript as submitted: all authors. Guarantor of the article: MST.

  • Funding This study was supported by the National Institutes of Health (NIH) grants R01 DK058088, R01 DK117809, and R01 DK082412 to MST, and the Department of Defense grant W81XWH2010134 (PR192583) to ZJ and MST.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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