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Monocyte Chemoattractant Protein-1-Induced Protein-1 (MCPIP1) knockout mouse

Invented by Jerzy Kotlinowski , Natalia Pydyn , Edyta Kus , Stefan Chlopicki , Jolanta Jura
Invented at Jagiellonian University
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From Kotlinowski J. et al. bioRxiv; 2020. DOI: 10.1101/2020.09.05.250522: Comparison between characteristics of human PBC and Mcpip1(AlbKO) mice
From Kotlinowski J. et al. bioRxiv; 2020. DOI: 10.1101/2020.09.05.250522: Progression of intrahepatic bile duct pathology in the liver parenchyma of 6 to 52-week-old Mcpip1(AlbKO) male mice. Proliferative changes in intrahepatic bile ducts with inflammatory infiltration predominate in young (6-week-old) mice leading to bile duct destruction, intraductal obstruction, and extensive fibrosis. At the age of 24 weeks, the processes of proliferation, inflammation, and collagen deposition were reduced, while aging mice (52-week-old) developed new foci of cholangiocyte proliferation accompanied by active fibrotic areas. Magnification 200x, HE (AD) and PSR (E-H) staining. HE, hematoxylin and eosin; PSR, picrosirius red.
From Kotlinowski J. et al. bioRxiv; 2020. DOI: 10.1101/2020.09.05.250522 Characterization of hallmarks of primary biliary cholangitis in Mcpip1AlbKO mice HE staining of 52-week old mice showing (A) Proliferation of intrahepatic bile ducts with associated parenchymal inflammation; (B) Epithelial destruction of intrahepatic bile ducts (black arrows) and extensive fibrosis of parenchyma; (C) Resolution of inflammation in intrahepatic bile ducts involving macrophages (black arrows); (D) Dysplasia of cholangiocytes with associated intraductal obstruction of intrahepatic bile ducts (asterisks); (E) Cholestasis and bile acid deposition in hepatocytes; (F) Small granuloma (white arrows indicate hepatocyte necrosis), magnification 400x. (G) Collagen area in the liver of 6, 12, 24, and 52-week-old Mcpip1fl/fl and Mcpip1AlbKO mice; (H) Number of bile ductules in livers per high power field (HPF); Concentrations of total IgG (I) and IgM (J) classes in plasma of 6 and 24-week-old Mcpip1fl/fl and Mcpip1AlbKO mice; (K) Percentage of Mcpip1AlbKO mice, with higher concentration of anti-PDC-E2 antimitochondrial autoantibodies and anti-gp-210 antinuclear autoantibodies compared to mean concentration in control Mcpip1fl/fl counterparts. Data represent mean ± SEM, *p<0.05, ***p < 0.001 vs. Mcpip1 fl/fl; #p < 0.05, ##p < 0.01; ###p < 0.001 vs. 6 weeks. H&E, hematoxylin and eosin.
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Catalogue Number 160590
Antigen/Gene or Protein Targets Monocyte Chemoattractant Protein-1-Induced Protein-1
Disease Keywords human primary biliary cholangitis
Synonyms Regnase1, Zc3h12a
Model Knock-Out
Relevance Adapted from Kotlinowski J. et al. bioRxiv; 2020. DOI: 10.1101/2020.09.05.250522:
Primary biliary cholangitis (PBC) is an autoimmune disease characterized by progressive destruction of the intrahepatic bile ducts. The immunopathology of PBC involves excessive inflammation; therefore, negative regulators of inflammatory response, such as Monocyte Chemoattractant Protein-1-Induced Protein-1 (MCPIP1, alias Regnase1) may play important roles in the development of PBC.
Research Area Autoimmunity
Notes Adapted from Kotlinowski J. et al. bioRxiv; 2020. DOI: 10.1101/2020.09.05.250522:
This mouse model was developed to verify whether Mcpip1 expression protects against development of PBC. Deletion of hepatic Mcpip1 in Mcpip1AlbKO mice leads to development of PBC that recapitulates phenotype of human patients. These animals, show early prenatal origin and age-dependent progression of the disease.

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Deletion of Mcpip1 in Mcpip1AlbKO mice recapitulates the phenotype of human primary biliary cholangitis

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References: 1 entry

Deletion of Mcpip1 in Mcpip1AlbKO mice recapitulates the phenotype of human primary biliary cholangitis

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Inventor Information

Inventors

Jerzy Kotlinowski

Jerzy Kotlinowski

Natalia Pydyn

Natalia Pydyn

Edyta Kus

Edyta Kus

Stefan Chlopicki

Stefan Chlopicki

Jolanta Jura

Jolanta Jura

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Invented at

Jagiellonian University
Jagiellonian University

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