26vzmnrw114 10.3205/26vzmnrw114 urn:nbn:de:0183-26vzmnrw1149 Meeting Abstract First results of a liver-specific Nope knockout mouse model Zweerink Zweerink S. S
University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany University of Cologne, Center of molecular medicine cologne, Cologne, Germany
author Schulte Schulte S. S
University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany
author Konze Konze E. E
University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany University of Cologne, Center of molecular medicine cologne, Cologne, Germany
author Jakob Jakob B. B
University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany University of Cologne, Center of molecular medicine cologne, Cologne, Germany
author Schmitt Schmitt S. S
University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany University of Cologne, Center of molecular medicine cologne, Cologne, Germany
author Troeder Troeder S. S
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
author Zevnik Zevnik B. B
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
author Lackmann Lackmann J.-W. JW
University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany University of Cologne, Center of molecular medicine cologne, Cologne, Germany
author Neumann-Haefelin Neumann-Haefelin C. C
University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany University of Cologne, Center of molecular medicine cologne, Cologne, Germany
author Nierhoff Nierhoff D. D
University Hospital of Cologne, Clinic for Gastroenterologie und Hepatologie, Cologne, Germany
author German Medical Science GMS Publishing House
Düsseldorf
 610 20260618 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0644 114 Niederrheinisch-Westfälische Gesellschaft für Chirurgie Gesellschaft für Gastroenterologie in Nordrhein-Westfalen e.V. 192. Jahrestagung der Niederrheinisch-Westfälischen Gesellschaft für Chirurgie, 34. Jahrestagung der Gesellschaft für Gastroenterologie Viszeralmedizin NRW 2026 Gastroenterologie Dortmund 20260618 20260619 114 TextBackground 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. 0 0 0 0