Biocytogen’s MASH Models: Accelerating Therapeutic Discovery in Metabolic Liver Disease
Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as NASH, is a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD) and a leading cause of chronic liver disease worldwide. Marked by hepatic fat accumulation, inflammation, and hepatocyte injury, MASH can progress to fibrosis, cirrhosis, or hepatocellular carcinoma—especially in individuals with obesity, type 2 diabetes, or metabolic syndrome (Tacke et al. 2023; Savari and Mard 2024).
Despite its high prevalence, effective treatments have only recently begun to emerge, highlighting an urgent need for new therapeutic strategies. To address this, Biocytogen is developing a portfolio of advanced MASH mouse models—including induced disease models with drug-target humanized mice and models with genetic alterations that mimic disease—to better capture disease mechanisms and accelerate next-generation drug discovery.
Therapeutic Targets in MASH
GPR75: A Genetic Regulator of Lipid Metabolism
G protein-coupled receptor 75 (GPR75) has attracted significant attention as a therapeutic target for reducing hepatic lipid accumulation (Hardwick et al. 2025). Loss-of-function mutations in GPR75 are associated with lower body fat percentages in humans and mice, indicating a protective role against obesity and related metabolic conditions. In murine models, GPR75 deletion leads to decreased hepatic triglyceride levels and improved glucose homeostasis, suggesting a critical role in energy balance (Leeson-Payne et al. 2024).
GLP-1 Receptor Agonists: Clinically Validated Metabolic Modulators
Glucagon-like peptide-1 receptor (GLP-1R) agonists are widely used to treat type 2 diabetes and obesity. These agents mimic endogenous GLP-1, enhancing insulin secretion, suppressing glucagon release, delaying gastric emptying, and promoting satiety. Their actions result in improved glycemic control and weight loss, making them attractive for managing metabolic components of MASH (Bifari et al. 2018; Zheng et al. 2024).
CIDEB and DGAT2: Emerging Targets in Lipid Regulation
Targeting CIDEB and DGAT2 offers promising therapeutic avenues in MASH. CIDEB, a lipid droplet-associated protein, facilitates lipid droplet fusion and VLDL maturation. Loss-of-function mutations in CIDEB are associated with reduced VLDL lipidation and protection against steatohepatitis (Chen et al. 2020). DGAT2 catalyzes the final step in triglyceride synthesis. Inhibiting DGAT2 reduces hepatic triglyceride accumulation, highlighting its therapeutic potential (Amin et al. 2019).
Accelerating MASH Therapeutics with Biocytogen’s Mouse Models
Biocytogen’s advanced MASH mouse models replicate key features of human disease—lipid metabolism dysregulation, chronic inflammation, insulin resistance, and fibrosis—enabling robust preclinical evaluation of new therapies.
In addition, we offer featured humanized mice for MASH-related targets such as GPR75, GLP1R, GLP1R/hGCGR, GCGR, GIPR, CIDEB, DGAT2, and HSD17B13, as well as knockout models such as B-Gpr75 KO mice to explore protective loss-of-function mechanisms, offering a powerful platform for gene-targeted intervention research.
Case Study 1: Gpr75 Knockout Mice Resist High-Fat Diet-Induced Obesity
C57BL/6, B-hGPR75 (human gene knock-in), and Gpr75 knockout (KO) mice were fed a high-fat diet for 10 weeks. Epididymal fat, inguinal fat, and liver weights increased significantly in C57BL/6 and B-hGPR75 mice compared to chow-fed controls, while Gpr75 KO mice showed no such changes. Mean ± SEM.
Case Study 2: Orforglipron Enhances Glucose Tolerance and Insulin Secretion in Humanized GLP1R Mice
B-hGLP1R mice and C57BL/6 mice received Orforglipron (1 mg/kg, p.o., –30 min) followed by intraperitoneal glucose tolerance testing (2 g/kg glucose, IPGTT). Orforglipron enhanced glucose clearance (A) and plasma insulin secretion (B) in B-hGLP1R mice plus, but not in C57BL/6 mice. Mean ± SEM.
Case Study 3: Efficient Knockdown of Human CIDEB by siRNA in Humanized Mice
Homozygous B-hCIDEB mice were treated with human CIDEB-targeting or control siRNA and sacrificed on day 7 or 21. Liver tissues were collected to quantify human CIDEB mRNA expression by qPCR. (A) Experimental design schematic.(B) siRNA significantly reduced hepatic CIDEB mRNA levels. Mean ± SEM.
Case Study 4: Protein Expression in Humanized DGAT2 Mice
Western blot analysis of DGAT2 protein expression in various tissues from wild-type C57BL/6JNifdc (+/+) and homozygous B-hDGAT2 (H/H) mice. DGAT2 was detected in liver and adipose tissues of both strains using a cross-reactive anti-DGAT2 antibody (Proteintech, 17100-1-AP). H: Humanized.
Biocytogen’s humanized models of key MASH-related genes—including GPR75, GLP-1R, CIDEB, DGAT2, and more—deliver unparalleled precision for preclinical research in metabolic liver diseases.