Susceptibility and transcriptional characteristics of inbred C57BL/6J and outbred ICR mice in CDAHFD-induced MASH models.

Abstract

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive fibrotic liver disease, the underlying mechanisms of which have not been fully elucidated. Most MASH research relies on diet-induced models, particularly inbred mouse strains such as C57BL/6J. Although inbred strains are commonly used, outbred mice more accurately reflect the genetic diversity of human populations. It was reported that ICR mice were resistant to developing MASH after high-fat diet feeding. However, the effects of choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) on ICR mice remain unexplored. The CDAHFD is a widely adopted diet-induced model for MASH. In this study, C57BL/6J and ICR mice were fed either a normal diet (ND) or a CDAHFD for 10 weeks. Metabolism-related phenotypes and liver histology assessments were conducted to establish MASH models. RNA transcriptome sequencing of liver samples was performed to identify differentially expressed genes, which were then aligned to the human MASH transcriptome. RESULTS: We successfully established MASH models via CDAHFD in both C57BL/6J and ICR mouse strains. ICR mice presented transcriptional profiles comparable to those of the C57BL/6J strain and effectively replicated the inflammatory and fibrotic features observed in patients with MASH. CONCLUSIONS: This study revealed that ICR mice are as suitable as inbred C57BL/6J mice for CDAHFD-induced MASH models.