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Characterization of hepatocyte‐specific SRSF1 (SF2/ASF) knockout mice
Author(s) -
Langiewicz Magda,
Sen Supriya,
Webster Nicholas J
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.922.15
Subject(s) - rna splicing , alternative splicing , exon , biology , splicing factor , knockout mouse , minigene , conditional gene knockout , microbiology and biotechnology , genetics , gene , phenotype , rna
Alternative splicing is widely believed to have a major impact on almost all biological processes since it increases proteome complexity and thereby controls protein function. SRSF1 (SF2/ASF) is a member of the SR protein family, which are essential for constitutive splicing and fulfilling regulatory functions in alternative splicing. Previously, we have shown that SRSF1 binds to the alternatively spliced exon 11 of the insulin receptor ( INSR ) and promotes its incorporation in hepatoma cells. To demonstrate the physiological importance of alternative splicing to the regulation of metabolism, we created a hepatocyte‐specific knockout of SRSF1 (SRSF1LKO) by crossing SRSF1 flox/flox mice with albumin‐cre mice, which specifically express the cre recombinase in adult hepatocytes. Mice are born in the expected mendelian ratio and do not show any growth retardation unlike the hepatocytes specific SRSF3 knockout that we have previously characterized. We will present data showing efficient tissue specific deletion of the SRSF1 allele, the reduction in SRSF1 expression , and alterations in INSR splicing. We will also present data on the metabolic and physiological parameters and liver morphology between SFSR1LKO and littermate control mice, as well as alterations in global gene expression and splicing by exon array analysis. SFSR1LKO is an important model to study alternative splicing in vivo . Supported by a Merit Review Award from the Department of Veterans Affairs.