This study investigates the interplay between the PIDDosome complex and SCAP in regulating the progression from simple steatosis to steatohepatitis under a high-fructose diet. Using hepatocyte-specific Knockout mouse models for SCAP and PIDDosome components, the researchers demonstrate that SCAP ablation prevents simple steatosis but exacerbates ER stress and liver damage when combined with a high-fructose diet. Conversely, PIDDosome ablation reduces ER stress and protects against steatohepatitis, highlighting the antagonistic roles of these pathways in liver disease progression.
SCAP ablation inhibits simple steatosis but increases susceptibility to steatohepatitis under high-fructose diet due to enhanced ER stress. PIDDosome component ablation mitigates ER stress and protects against liver damage, suggesting potential therapeutic targets for preventing NASH progression.
Hepatocyte-specific SCAP Knockout (Scap^ΔHep) and PIDDosome component Knockouts (e.g., Casp2^−/−, Pidd1^−/−)
Non-alcoholic fatty liver disease (NAFLD), Non-alcoholic steatohepatitis (NASH), ER stress, Lipid metabolism, Hepatic inflammation
Conditional Knockout models, Hepatocyte-specific gene deletion, Albumin-Cre driver, High-fructose diet-induced liver disease, ER stress modulation
From model design to experimental results
Tailor-made solutions adapted to scientific questions
Comprehensive dataset package
Generated with biopharma partners and in-house
Scientific follow-up and advice along the project
Collaborative approach for problem solving and development of innovative models
Breeding facilities in US and Europe
Certified health status from professional breeders
