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Int J Biol Sci 2015; 11(11):1248-1256. doi:10.7150/ijbs.13011

Research Paper

Adapted Resistance to the Knockdown Effect of shRNA-Derived Srsf3 siRNAs in Mouse Littermates

Masahiko Ajiro1, Rong Jia1,3, Rui-Hong Wang2,4, Chu-Xia Deng2,4, Zhi-Ming Zheng1✉

1. Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA
2. Genetics of Development and Disease Branch, 10/9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, MD 20892, USA.
3. Wuhan University School of Stomatology, Wuhan, Hubei, China
4. Faculty of Health Sciences, University of Macau, Macau SAR, China

Abstract

Gene silencing techniques are widely used to control gene expression and have potential for RNAi-based therapeutics. In this report, transgenic mouse lines were created for conditional knockdown of Srsf3 (SRp20) expression in liver and mammary gland tissues by expressing Srsf3-specific shRNAs driven by a U6 promoter. Although a small portion of the transgenic mouse littermates were found to produce siRNAs in the targeted tissues, most of the transgenic littermates at two months of age failed to display a knockdown phenotype of Srsf3 expression in their liver and mammary gland tissues where an abundant level of Srsf3 siRNAs remained. We saw only one of four mice with liver/mammary gland expressing Srsf3 siRNA displayed a suppressed level of Srsf3 protein, but not the mRNA. Data indicate that the host resistance to a gene-specific siRNA targeting an essential gene transcript can be developed in animals, presumably as a physiological necessity to cope with the hostile perturbation.

Keywords: Srsf3, shRNAs, transgenic mouse

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How to cite this article:
Ajiro M, Jia R, Wang RH, Deng CX, Zheng ZM. Adapted Resistance to the Knockdown Effect of shRNA-Derived Srsf3 siRNAs in Mouse Littermates. Int J Biol Sci 2015; 11(11):1248-1256. doi:10.7150/ijbs.13011. Available from http://www.ijbs.com/v11p1248.htm