Double-Knockout Animal Model for NAFLD Progression
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Solution Overview
Problem
Current methods for modeling non-alcoholic liver disease (NAFLD) are inefficient, as they require high-fat diets and take longer to induce liver cancer, lacking a reliable animal model for screening therapeutic agents effectively.
Innovation Solution
A double-knockout animal model with Pten and Sav1 genes knocked out specifically in the liver, which accelerates the progression of NAFLD to liver cancer, allowing for the screening of therapeutic agents by measuring the expression levels of YAP, TAZ, IRS2, and AKT proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If high-fat diet is used to induce NAFLD in animal models, then liver disease progression is achieved, but the time required to develop liver cancer is extended and the model becomes less efficient
Solution Approach 1:
The patent changes the genetic parameters of the animal model by knocking out Pten and Sav1 genes specifically in the liver, which accelerates the progression from NAFLD to liver cancer without requiring high-fat diet intervention, thereby reducing the time required and improving modeling efficiency
Solution Approach 2:
The patent performs preliminary genetic modification (knockout of Pten and Sav1 genes) before disease induction, which pre-configures the animal model to rapidly progress through NAFLD stages and develop liver cancer faster than conventional models, eliminating the need for prolonged high-fat diet feeding
2Reliability
If conventional NAFLD animal models are used, then disease modeling is achieved, but they lack reliability for effective therapeutic agent screening
Solution Approach 1:
The patent establishes a feedback mechanism by measuring the expression levels of YAP, TAZ, IRS2, and AKT proteins to monitor the progression of NAFLD and response to therapeutic agents, enabling reliable screening and evaluation of treatment effectiveness
Solution Approach 2:
The patent replaces the mechanical/dietary induction method (high-fat diet) with a genetic mechanism (Pten and Sav1 knockout) that more reliably mimics human NAFLD pathogenesis, thereby improving the model's reliability for therapeutic screening while maintaining operational simplicity
Data Source
AI summary
The present invention provides a method of manufacturing an animal model of non-alcoholic liver disease by using correlation among metabolic dysregulations through AKT regulation by Hippo signaling, and an animal model prepared by the method above, and a screening method of a therapeutic agent by using the animal model.