RT Journal Article T1 RNAi-Mediated Knockdown of IKK1 in Transgenic Mice Using a Transgenic Construct Containing the Human H1 Promoter A1 Moreno Maldonado, Rodolfo A1 Murillas, Rodolfo A1 Navarro, Manuel A1 Page, Angustias A1 Suárez Cabrera, Cristian A1 Alameda, Josefa P. A1 Bravo Moral, Ana María A1 Llanos Casanova, M. A1 Ramírez, Ángel AB Inhibition of gene expression through siRNAs is a tool increasingly used for the study of gene function in model systems, includingtransgenic mice. To achieve perdurable effects, the stable expression of siRNAs by an integrated transgenic construct is necessary.For transgenic siRNA expression, promoters transcribed by either RNApol II or III (such as U6 or H1 promoters) can be used.Relatively large amounts of small RNAs synthesis are achieved when using RNApol III promoters, which can be advantageous inknockdown experiments. To study the feasibility of H1 promoter-driven RNAi-expressing constructs for protein knockdown intransgenic mice, we chose IKK1 as the target gene. Our results indicate that constructs containing the H1 promoter are sensitiveto the presence of prokaryotic sequences and to transgene position effects, similar to RNApol II promoters-driven constructs. Weobserved variable expression levels of transgenic siRNA among different tissues and animals and a reduction of up to 80% in IKK1expression. Furthermore, IKK1 knockdown led to hair follicle alterations. In summary, we show that constructs directed by the H1promoter can be used for knockdown of genes of interest in different organs and for the generation of animal models complementaryto knockout and overexpression models. PB Hindawi SN 2356-6140  YR 2014 FD 2014 LK http://hdl.handle.net/10347/21653 UL http://hdl.handle.net/10347/21653 LA eng NO Moreno-Maldonado, R., Murillas, R., Navarro, M., Page, A. et al. (2014). RNAi-Mediated Knockdown of IKK1 in Transgenic Mice Using a Transgenic Construct Containing the Human H1 Promoter. "The Scientific World Journal", 193803 NO This research was supported by Grants from the Spanish government (Ministerio de Economía y Competitividad: SAF2010-22156 to Angel Ramirez and PI10/01480 to M. Llanos Casanova and Instituto de Salud Carlos III: RD12/0036/0009) and from the Comunidad Autonoma de Madrid (52011/BMD2470) DS Minerva RD 4 may 2026