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Hereditary pancreatitis model by blastocyst complementation in mouse.

Ayumu Asai1,2,3, Masamitsu Konno1,2,3, Koichi Kawamoto3

  • 1Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan.

Oncotarget
|June 18, 2020
PubMed
Summary

Researchers used the blastocyst complementation method to model human hereditary pancreatitis. This technique successfully reproduced pancreatic disorders in mice, offering a new way to study complex human diseases.

Keywords:
PRSS1blastocyst complementationdisease-specific pluripotent stem cellshereditary pancreatitis

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Area of Science:

  • Stem cell biology
  • Developmental biology
  • Genetics

Background:

  • Pluripotent stem cells aid in understanding human disease mechanisms.
  • Generating organ-specific cells like pancreas and liver in vitro remains challenging.
  • Modeling human hereditary pancreatitis (HP) has been unfeasible.

Purpose of the Study:

  • To investigate the mechanisms of human hereditary pancreatitis (HP).
  • To evaluate the utility of the blastocyst complementation (BC) method for modeling pancreatic disorders.

Main Methods:

  • Employed the blastocyst complementation (BC) method.
  • Injected mouse embryonic stem (ES) cells with CRISPR/CAS9-mediated Prss1 gene mutations into Pdx1-deficient blastocysts.
  • Pdx1 is a critical transcription factor for pancreas development.

Main Results:

  • Successfully generated Prss1-mutant mice exhibiting extremely activated trypsin.
  • The mouse phenotype accurately mimicked human hereditary pancreatitis.
  • The BC method proved effective for reproducing and studying pancreatic disorders.

Conclusions:

  • The blastocyst complementation method is a viable tool for modeling pancreatic disorders.
  • This approach facilitates the investigation of uncharacterized human diseases.
  • Opens new avenues for studying hereditary pancreatitis and other complex genetic conditions.