Mouse Models Targeting Selenocysteine tRNA Expression for Elucidating the Role of Selenoproteins in Health and Development

Bradley A Carlson,Dolph L Hatfield,Petra A Tsuji,Vadim N Gladyshev,Min-Hyuk Yoo

doi:10.3390/molecules14093509

Abstract

Selenium (Se) deficiency has been known for many years to be associated with disease, impaired growth and a variety of other metabolic disorders in mammals. Only recently has the major role that Se-containing proteins, designated selenoproteins, play in many aspects of health and development begun to emerge. Se is incorporated into protein by way of the Se-containing amino acid, selenocysteine (Sec). The synthesis of selenoproteins is dependent on Sec tRNA for insertion of Sec, the 21st amino acid in the genetic code, into protein. We have taken advantage of this dependency to modulate the expression of Sec tRNA that in turn modulates the expression of selenoproteins by generating transgenic, conditional knockout, transgenic/standard knockout and transgenic/conditional knockout mouse models, all of which involve the Sec tRNA gene, to elucidate the intracellular roles of this protein class.

Highlights

Selenium (Se) is an essential element in the diet of many life forms including humans and other mammals
We have taken advantage of the fact that selenoprotein expression can be controlled by manipulating the expression of Sec tRNA[Ser]Sec to generate a number of mouse models for elucidating the intracellular roles of selenoproteins [9,10,11,12], which is the subject of this review
This study provided additional evidence that the Sec tRNA[Ser]Sec population is not limiting in selenoprotein synthesis

Summary

Introduction

Selenium (Se) is an essential element in the diet of many life forms including humans and other mammals. To study the intracellular roles of selenoproteins using Sec tRNA[Ser]Sec as a tool to manipulate the expression of this Se-containing protein class, we have developed mouse models that encode (1) wild type or mutant transgenes [9], (2) a conditional knockout of Trsp [11], or (3) a combination of a standard knockout of Trsp and mutant or wild type transgenes or a conditional knockout of Trsp and mutant or wild type transgenes [10,28]. Each of these mouse models and their uses are further discussed below

Trsp transgenic mouse models

Major Findings

Trsp conditional knockout mouse models

Mouse models relating to human disease

Other mouse models involving Trsp

Conclusions