Characterization of Hepatocyte-Specific CD73 Knockout Mice

Undergraduates: Deekshita Ramanarayanan, Karel Alcedo Dr. Natasha T. Snider Deekshita Ramanarayanan

Faculty Advisor: Natasha Snider
Department: Biology

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Chronic liver injury is one of the fastest growing pathologies in the United States. CD73, or ecto-5¿¿¿-nucleotidase (NT5E), has been linked to liver injury in recent years. CD73 is a membrane protein that catalyzes the conversion of extracellular AMP to adenosine, and has been found to be upregulated in several human carcinomas. It was discovered to play a role in drug induced liver injury, and was also shown to have protective effects in ethanol-induced hepatic steatosis as well as other hepatocyte-specific injury. In order to determine the liver-specific function of CD73, we generated a hepatocyte-specific CD73 knockout mouse model using the cre/lox system. We characterized the properties of this mouse model through Western Blot, serum profiling, qPCR and enzyme histochemistry. We found that CD73 knockout mice were more prone to fatty livers, and to developing hepatic steatosis at a later age without inducing injury. We also found that the female knockout mice had decreased albumin levels, which is indicative of potentially compromised liver function. Through qPCR analysis, we found that components of the AP1 transcription factor complex are more highly expressed in the knockout mice. Characterization of these hepatocyte-specific knockout mice may result in determining the tissue specific or the non-enzymatic function of CD73, which would prove useful in targeting CD73 for therapy in different disease states.