ISSN: 1449-2288International Journal of Biological Sciences
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Int J Biol Sci 2008; 4(4):202-207. doi:10.7150/ijbs.4.202 This issue Cite
Research Paper
Generation and Validation of a Mouse Line with a Floxed SRC-3/AIB1 Allele for Conditional Knockout
1. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
2. Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA
# Z. Liu and L. Liao contributed equally to this work.
Abstract
The steroid receptor coactivator-3 (SRC-3), also known as AIB1, ACTR, p/CIP and NCOA3, is a transcriptional coactivator for nuclear receptors and certain other transcription factors. SRC-3 is widely expressed and plays important physiological functions and pathogenic roles in breast and prostate cancers. SRC-3 knockout (SRC-3-/-) mice display genetic background-dependent embryonic lethality and multiple local and systemic abnormalities. Since both the partial lethality and the systemic effects caused by global SRC-3 knockout interfere with downstream investigation of tissue-specific function of SRC-3, we have generated floxed SRC-3 (SRC-3f/f) mice with conditional alleles carrying loxP sites in introns 10 and 12 by a gene-targeting strategy. The two SRC-3f/f mouse lines (A and B) are indistinguishable from wild type mice. To test if deletion of the floxed exons 11 and 12 for SRC-3 nuclear receptor interaction domains and disruption of its downstream sequence for transcriptional activation domains would inactivate SRC-3 function, SRC-3f/f mice were crossbred with EIIa-Cre mice to generate SRC-3d/d mice with germ line deletion of the floxed SRC-3 gene. Both lines of SRC-3d/d mice exhibited growth retardation and low IGF-I levels, which was similar to that observed in SRC-3-/- mice. The line A SRC-3d/d mice showed normal viability, while line B SRC-3d/d mice showed partial lethality similar to SRC-3-/- mice, probably due to variable distributions of genetic background during breeding. These results demonstrate that the floxed SRC-3 mouse lines have been successfully established. These mice will be useful for investigating the cell type- and developmental stage-specific functions of SRC-3.
Keywords: SRC-3, AIB1 Allele, knockout mice
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