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    2. Viszeralmedizin NRW 2026. 192. Jahrestagung der Niederrheinisch-Westfälischen Gesellschaft für Chirurgie, 34. Jahrestagung der Gesellschaft für Gastroenterologie
    3. First results of a liver-specific Nope knockout mouse model
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Viszeralmedizin NRW 2026. 192. Jahrestagung der Niederrheinisch-Westfälischen Gesellschaft für Chirurgie, 34. Jahrestagung der Gesellschaft für Gastroenterologie


18.-19.06.2026
Dortmund

Meeting Abstract

First results of a liver-specific Nope knockout mouse model

S. Zweerink - University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany; University of Cologne, Center of molecular medicine cologne, Cologne, Germany
S. Schulte - University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany
E. Konze - University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany; University of Cologne, Center of molecular medicine cologne, Cologne, Germany
B. Jakob - University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany; University of Cologne, Center of molecular medicine cologne, Cologne, Germany
S. Schmitt - University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany; University of Cologne, Center of molecular medicine cologne, Cologne, Germany
S. Troeder - University of Cologne, Cluster of excellence cellular stress responses in aging-associated diseases, Cologne, Germany; Faculty of Medicine and University Hospital, University of Cologne, In vivo research facility, Cologne, Germany
B. Zevnik - University of Cologne, Cluster of excellence cellular stress responses in aging-associated diseases, Cologne, Germany; Faculty of Medicine and University Hospital, University of Cologne, In vivo research facility, Cologne, Germany
J.-W. Lackmann - University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany; University of Cologne, Center of molecular medicine cologne, Cologne, Germany
C. Neumann-Haefelin - University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany; University of Cologne, Center of molecular medicine cologne, Cologne, Germany
D. Nierhoff - University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany

Text

Background and objective: Neighbor of Punc E11 (Nope) is a known oncofetal marker in the liver. To understand the function of this membrane protein that is preferentially expressed by epithelial cells, we developed a liver-specific Nope knockout (KO) mouse.

Method: We generated the NopeKO mouse using CRISPR-Cas9 and the liver-specific Alfp-promoter for Cre-recombinase expression. The phenotype of NopeKO was analyzed macroscopically and microscopically using biomolecular methods such as qPCR, immunofluorescence microscopy (IF) and discovery proteomics.

Result: The liver-specific NopeKO mice were viable and had a normal liver/body ratio of 3% one week postnatally (1wpn) and 5% at 3 wpn. At 1wpn, Nope RNA levels were reduced by more than 75% and at 3 wpn by more than 80%. IF showed that Nope was expressed by macrophages and endothelial cells and not by epithelial cells e.g. hepatocytes and cholangiocytes. Whole proteome analysis showed significant changes in protein abundance. At 1wpn, 20 proteins showed differential expression, with 11 showing higher and 9 showing lower expression levels in NopeKO (cut-off 4-fold) compared to controls. At 3 wpn, 23 proteins showed differential expression, with 14 showing higher and 9 showing lower expression levels in NopeKO. 11 proteins were associated with lipogenesis and 13 with HCC.

Summary: We generated a viable knockout mouse model for the oncofetal marker Nope and identified different protein expression levels in the early postnatal period. In subsequent studies, we will able to focus on the effects of Nope on liver metabolism and oncogenesis.