Creating a mouse model for SECISBP2 syndrome

SECISBP2 is pivotal in the biosynthesis of proteins containing the amino acid selenocysteine (Sec). Incorporation of Sec into the 25 selenoproteins of the human genome requires a specific translational machinery, including a UGA codon and a stem loop structure in the 3′‐UTR, the SECIS element. SECISBP2 is a high‐affinity SECIS binding protein that is also of major importance for proper selenoprotein translation. Mutations in SECISBP2 lead to growth retardation, myopathy and hearing impairement, which can be attributed to specific selenoprotein deficiencies. Creation of Secisbp2 null mice as a model for the SECISBP2 syndrome resulted in embryonic lethality resembling thioredoxin reductase‐deficient mice. Heterozygous Secisbp2 mice show only mild changes in selenoprotein expression. To elucidate the possible role of alternative SECIS binding proteins that may act in parallel, we created conditional Secisbp2 mice. Hepatocyte‐specific ablation of Secisbp2 did not impair survival, but reduced expression of selenoproteins. Neuron‐specific inactivation created a milder phenotype than inactivation of tRNA(Sec). These results indicate that selenoproteins are differentially affected by the absence of Secisbp2.