A novel liver-specific knock-out mouse to investigate human alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH).

Description of projects available to graduate students:
The incidence of ALD and NASH is very high among the humans and is expected to rise in the coming years. There are no reliable animal models of ALD and NASH that mimic all of the characteristics of human diseases. As a result, there are no satisfactory diagnostic procedures for early detection and therapies for ALD or NASH. It is also important to note that only a subpopulation of humans is vulnerable to developing ALD or NASH. Very recently, we developed a liver-specific conditional knockout mouse for augmenter of liver regeneration (ALR) that exhibits all of the characteristics of NASH, and this phenotype is also highly susceptible to acute and chronic alcoholic liver injury. Our human data show that ALR levels are very low in livers of subjects with advanced ALD and NASH thus strongly indicating that the results from the liver-specific knockout mouse will have high relevance to the human diseases. These results also indicate that genetic defect in ALR or ALR deficiency renders humans vulnerable to developing ALD and NASH.

Techniques graduate student will learn:
In these two independent projects, the student will be involved in biochemical and molecular characterization of the ALR-KO mouse, will learn methods and assays of induction of ALD or NASH, and biochemical/molecular pathways associated with the development of these clinically challenging fatal diseases using ALR-KO and ALR+/- mice.