Mouse models for assessing the role of selenoproteins in health and development

Authors

Bradley A. Carlson, National Cancer Institute, National Institutes of Health, Bethesda, MDFollow
Xue-Ming Xu, National Cancer Institute, National Institutes of Health, Bethesda, MDFollow
Rajeev Shrimali, National Cancer Institute, National Institutes of Health, Bethesda, MD
Aniruddha Sengupta, National Cancer Institute, National Institutes of Health, Bethesda, MD
Min-Hyuk Yoo, National Cancer Institute, National Institutes of Health, Bethesda, MD
Nianxin Zhong, National Cancer Institute, National Institutes of Health, Bethesda, MD
Dolph L. Hatfield, National Cancer Institute, National Institutes of Health, Bethesda, MDFollow
Robert Irons, National Cancer Institute, National Institutes of Health, Bethesda, MD
Cindy D. Davis, National Cancer Institute, National Institutes of Health, Bethesda, MD
Byeong Jae Lee, Seoul National UniversityFollow
Sergey V. Novoselov, University of Nebraska-Lincoln
Vadim N. Gladyshev, University of Nebraska-LincolnFollow

Date of this Version

June 2006

Comments

Published in Selenium: Its Molecular Biology and Role in Human Health, Second Edition, edited by Dolph L. Hatfield, Marla J. Berry, and Vadim N. Gladyshev. Springer, 2006.

Abstract

Mouse models have been generated to assess the roles of selenoproteins involved with housekeeping tasks and/or stress-related phenomena in development and health. Each mouse model has taken advantage of the fact that the synthesis of all selenoproteins is dependent on the expression of two selenocysteine ^{(Sec) tRNA[Ser]Sec} isoforms that differ fiom each other by a single methyl group on the ribosyl moiety at position 34. The endogenous ^{(Sec) tRNA[Ser]Sec} population was selectively altered by generating mouse models involving 1) transgenic animals carrying mutant or wild type ^{(Sec) tRNA[Ser]Sec} transgenes, 2) conditional knockout animals carrying a floxed ^{(Sec) tRNA[Ser]Sec} gene that was targeted for removal in specific tissues and organs using loxP-Cre technology and 3) transgenic/standard knockout animals carrying mutant or wild type transgenes and a knockout of the ^{(Sec) tRNA[Ser]Sec} gene wherein the animal's survival is dependent on the transgene. These mouse models perturbed selenoprotein expression, often in a protein- and tissue-specific manner, permitting us to better assess their function in health and development.