Analysis of the mouse selenoprotein P gene.

In vertebrates several proteins containing a covalently bound selenocysteine residue have been identified. Among these, selenoprotein P is the most unusual one: depending on the species, 8-12 selenocysteine residues are cotranslationally integrated into the polypeptide chain. The protein was traced in rat plasma, but its role has not been worked out so far. In order to improve our understanding on selenoprotein P we investigated its tissue-specific expression and its genomic DNA. RNA in situ hybridization analyses confirmed the liver-specific expression in mice. Selenoprotein P was also found to be expressed in testis, brain, gut, and hematopoietic cells. The murine selp gene contains five exons within 10.3 kb with a coding sequence restricted to exons 2 to 5. The complete gene including the selp promoter was sequenced. One TATA motif 38 bp upstream to exon 1 suggests transcription of selp by RNA polymerase II. Within the 1116 bp upstream of exon 1 four hepatic nuclear factor 3beta (HNF3beta) binding motifs were found, which is in line with liver-specific expression of selenoprotein P. The expression in hematopoietic cells might be due to multiple GATA-1 motifs. Two BRN-2 motifs suitable for the binding of brain-specific regulatory factors correlated to the selenoprotein P expression in the cerebellum. Selenoprotein P was also expressed in Leydig cells which could be regulated by binding proteins docking to the SRY motifs present in the promoter region.