title: Adapted Resistance to the Knockdown Effect of shRNA-Derived Srsf3 siRNAs in Mouse Littermates.
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.
authors.affiliation: 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.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ajiro
authors.affiliation: 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 ; 3. Wuhan University School of Stomatology, Wuhan, Hubei, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jia
authors.affiliation: 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. ; 4. Faculty of Health Sciences, University of Macau, Macau SAR, China.
authors.forename: Rui-Hong
authors.initials: RH
authors.lastname: Wang
authors.affiliation: 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. ; 4. Faculty of Health Sciences, University of Macau, Macau SAR, China.
authors.forename: Chu-Xia
authors.initials: CX
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Zheng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D020868:Gene Silencing / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068103:Serine-Arginine Splicing Factors
chemical_list: D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C106161:Srsf3 protein, mouse; D000068103:Serine-Arginine Splicing Factors
keywords: Srsf3; shRNAs; transgenic mouse