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Generation and Characterization of SRSF1 Hepatocyte- specific knockout mice (SRSF1HKO)


SR family RNA binding proteins regulate splicing of nascent RNAs in vitro but their physiological role in vivo is largely unexplored, as genetic deletion of many SR protein genes results in embryonic lethality. Here we show that SRSF1HKO mice ASF/SF2) have normal growth yet disrupted hepatocyte morphology. SRSF1HKO exhibit alterations in cell cycle regulation and lipid homeostasis characterized by heterogeneous hepatocyte populations, distorted glycogen storage, increased hepatic TG, and development of liver steatosis. The accumulation of lipids in the liver is associated with aging and is due to a decreased in triglyceride secretion but a normal rate of lipid synthesis. Our study provides the first evidence for a role of Srsf1 in morphological and functional differentiation of hepatocytes that may have relevance for human liver disease and metabolic dysregulation associated with a development of steatosis. SRSF1HKO is an essential mouse model in the pursuit of understanding the function of SR proteins in alternative splicing and its contribution to metabolic disease

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