This technology describes a mouse model for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) that develops phenotypes of the diseases at an early age without the need for toxic stimulation or associated metabolic abnormalities.
Existing small animal models of nonalcoholic fatty liver disease (NAFDL) and nonalcoholic steatohepatitis (NASH) require either high fat diets or toxic intervention to develop disease phenotypes. As NAFDL and NASH are associated with metabolic abnormalities, including insulin resistance, these animal models are not an ideal platform for assessing drugs that directly affect processes intrinsic to liver cells rather than metabolic processes. As such, there is a need for a small animal model of NAFDL and NASH that develops phenotypes of fatty liver disease without toxic intervention and without metabolic abnormalities associated with NAFDL and NASH.
This mouse model, known as the L-CKO mouse, has a liver cell-specific deletion of a nuclear membrane protein. This deletion results in phenotypes associated with nonalcoholic fatty liver disease (NAFDL) and nonalcoholic steatohepatitis (NASH), including stenosis and fat droplet accumulation within liver cells. Unlike other mouse models of NAFDL and NASH, which require toxic stimulation to induce disease phenotypes, L-CKO mice develop these phenotypes spontaneously. Importantly, in L-CKO mice, these phenotypes occur in the absence of metabolic abnormalities normally associated with fatty liver disease, such as insulin resistance.
This mouse model been experimentally validated to show tissue-specific phenotypes of NAFDL and NASH, following spontaneous disease development on a normal chow diet.
[Howard Worman, MD] (https://www.pathology.columbia.edu/profile/howard-j-worman-md)
IR CU17333
Licensing Contact: Jerry Kokoshka