The technology employs a hepatocyte-specific mouse model where the ALR gene, key for mitochondrial function and liver cell survival, is selectively deleted. This targeted gene alteration avoids the embryonic lethality seen in global knockouts while allowing for detailed study of liver development and disease progression. In these models, postnatal mice initially develop steatosis that regresses with hepatocyte death and regeneration, eventually leading to chronic inflammation, fibrosis, and liver cancer by one year of age. A complementary heterozygous model, with reduced ALR expression yet normal appearance, serves as an ideal platform for studying the liver’s response to stressors such as high-fat and alcohol-rich diets.
Description
The approach is differentiated by its precise mimicry of human liver disease progression, capturing the full spectrum from initial fatty liver to advanced fibrosis and cancer. Its dual-model strategy is uniquely suited for exploring both alcoholic and nonalcoholic steatohepatitis, providing unparalleled insights into the molecular mechanisms underlying these conditions. By reproducing the dynamic interplay between hepatocyte loss and regeneration, the technology offers a robust, reliable platform for testing therapeutic interventions and advancing our understanding of chronic liver diseases.
Applications
- Preclinical liver disease drug testing
- Liver toxicity screening platform
- NASH biomarker identification
- Liver cancer therapeutic evaluation
Advantages
- Accurately models human liver disease progression, including steatosis, fibrosis, and cancer development.
- Enables detailed investigation of ALR’s critical role in mitochondrial function and hepatocyte survival.
- Provides a platform to study liver responses to dietary factors and alcohol-induced stress.
- Facilitates research into the molecular mechanisms underlying nonalcoholic and alcoholic steatohepatitis.
- Offers robust preclinical models for testing potential therapeutic interventions for liver disorders.
IP Status
Research Tool
