PuSH - Publication Server of Helmholtz Zentrum München

da Silva Buttkus, P. ; Spielmann, N. ; Klein-Rodewald, T. ; Schütt, C. ; Aguilar-Pimentel, J.A. ; Amarie, O.V. ; Becker, L. ; Calzada-Wack, J. ; Garrett, L. ; Gerlini, R. ; Kraiger, M. ; Leuchtenberger, S. ; Östereicher, M.A. ; Rathkolb, B. ; Sanz-Moreno, A. ; Stoeger, C. ; Hölter, S.M. ; Seisenberger, C. ; Marschall, S. ; Fuchs, H. ; Gailus-Durner, V. ; Hrabě de Angelis, M.

Knockout mouse models as a resource for the study of rare diseases.

Mamm. Genome 34, 244-261 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Rare diseases (RDs) are a challenge for medicine due to their heterogeneous clinical manifestations and low prevalence. There is a lack of specific treatments and only a few hundred of the approximately 7,000 RDs have an approved regime. Rapid technological development in genome sequencing enables the mass identification of potential candidates that in their mutated form could trigger diseases but are often not confirmed to be causal. Knockout (KO) mouse models are essential to understand the causality of genes by allowing highly standardized research into the pathogenesis of diseases. The German Mouse Clinic (GMC) is one of the pioneers in mouse research and successfully uses (preclinical) data obtained from single-gene KO mutants for research into monogenic RDs. As part of the International Mouse Phenotyping Consortium (IMPC) and INFRAFRONTIER, the pan-European consortium for modeling human diseases, the GMC expands these preclinical data toward global collaborative approaches with researchers, clinicians, and patient groups.Here, we highlight proprietary genes that when deleted mimic clinical phenotypes associated with known RD targets (Nacc1, Bach2, Klotho alpha). We focus on recognized RD genes with no pre-existing KO mouse models (Kansl1l, Acsf3, Pcdhgb2, Rabgap1, Cox7a2) which highlight novel phenotypes capable of optimizing clinical diagnosis. In addition, we present genes with intriguing phenotypic data (Zdhhc5, Wsb2) that are not presently associated with known human RDs.This report provides comprehensive evidence for genes that when deleted cause differences in the KO mouse across multiple organs, providing a huge translational potential for further understanding monogenic RDs and their clinical spectrum. Genetic KO studies in mice are valuable to further explore the underlying physiological mechanisms and their overall therapeutic potential.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Benign Clinical-course; Warburg Micro Syndrome; Methylmalonic Aciduria; 17q21.31 Microdeletion; Rab3gap1 Mutations; Klotho; Bach2; Variants; Protein; Acsf3
ISSN (print) / ISBN 0938-8990
e-ISSN 1432-1777
Journal Mammalian Genome
Quellenangaben Volume: 34, Issue: 2, Pages: 244-261 Article Number: , Supplement: ,
Publisher Springer
Publishing Place One New York Plaza, Suite 4600, New York, Ny, United States
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Institute of Developmental Genetics (IDG)