Current mouse models fail to accurately recapitulate the progression of HNF1A-MODY diabetes, a type of diabetes caused by pathogenic mutations in a single gene. The team from Dr. Caroline Bonner (Inserm U1190/EGID, University/CHR of Lille, IPL), in collaboration with the Prof. Adrian Liston (KU Leuven and Cambridge), has developed a novel model that reproduces step by step the metabolic decline observed in the trajectory of human disease. This preclinical model reconstructs early insulin resistance and the liver complications (steatosis, fibrosis) as well as testosterone deficiency and progressive dysfunction of the pancreatic islets. Crucially, the researchers demonstrate that alpha cells are also altered, confirming that HNF1A-MODY is a bihormonal disorder. This new model offers a robust platform for testing innovative therapies against the disease and for furthering our understanding of prediabetes. This work represents a major advance for research on monogenic diabetes.
Progressive HNF1A-MODY pathophysiology revealed by a translational mouse model.
Isaline Louvet, Ana Acosta-Montalvo, Chiara Saponaro, Maria Moreno-Lopez, Sana Douffi, Abdelkrim El Karchaoui, Gianni Pasquetti, Julien Thevenet, Nathalie Delalleau, Valery Gmyr, Paolo Giacobini, Stéphanie Espiard, Julie Kerr-Conte, François Pattou, Adrian Liston, Caroline Bonner
JCI Insight. 2026;11(9):e198095. https://doi.org/10.1172/jci.insight.198095.
U1190 “Translational research on diabetes and metabolic diseases (RTD)"
Lille University Hospital – INSERM – University of Lille – Pasteur Institute of Lille
