Establishment and characterization of a metabolic dysfunction-associated steatotic liver disease model in the male Korean field mouse ( Apodemus peninsulae ): A comparison with the male C57BL/6J mouse

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly serious global health issue. The establishment of accurate animal models is crucial for elucidating its pathogenesis and developing effective therapeutic strategies. Although mouse models are widely used in MASLD research, they exhibit significant differences from humans in metabolic traits and disease progression, limiting their ability to fully recapitulate key pathological features of MASLD. In this study, we established an MASLD model in Apodemus peninsulae using a high-fat diet (HFD) and compared it with the commonly used C57BL/6J mouse model. The results showed that A. peninsulae developed marked lipid metabolism disorders and liver function impairment as early as week 4 with an HFD intervention. Histological analysis revealed progressive steatosis, inflammatory infiltration, and early fibrosis from weeks 8 to 16, which was confirmed by oil red O, Masson’s trichrome, and Sirius red staining. In contrast, pathological progression in C57Bl/6J mice was slower, with milder fibrosis. Immunolabeling and inflammatory cytokine expression further indicated a more intense inflammatory response in A. peninsulae. Overall, A. peninsulae offers advantages, such as rapid disease induction and stable phenotypes, making it a promising animal model for studying early-stage MASLD. Its shorter modeling period and more pronounced steatosis and liver injury suggest it more closely mimics the early pathological changes seen in human MASLD.