Phylogenetic development of a regulatory gene for the core 2 GlcNAc transferase in Mus musculus

In our previous study, we identified a mouse gene, Gsl5, that controls the expression of a glycolipid, GL-Y [Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Galbeta1-3)GalNAcbeta1-3Galalpha1-4Galbeta1-4Glcbeta1-Cer], and the core 2 structure of O-linked glycans of glycoproteins, GlcNAcbeta1-6(Galbeta1-3)GalNAcalpha-Ser/Thr, in a kidney tubular cell-specific manner through the regulation of UDP-GlcNAc beta-1,6-GlcNAc transferase (GNT). Regulation by the Gsl5 gene occurs at the level of GNT mRNA and the recessive allele of Gsl5 is rare and carried by DBA/2 and its related strains. Here, we report a sequence comparison of the 5' flanking region of the GNT gene among 5 laboratory strains and 10 wild-derived strains, demonstrating that the DBA/2 allele sequence is similar to the sequence carried by Asian Mus m. musculus and differs substantially from the East European M. m. musculus. These results suggest that the DBA/2 allele of Gsl5 was introduced into laboratory mouse strains by Asian wild-derived mice. Phylogenetic comparison of the 5' flanking region sequences between the recessive and dominant Gsl5 alleles indicates that mutations to create a functional Gsl5 gene occurred approximately one million years ago during the subspeciation of M. musculus, and provides a case for studies on the creation of functional genes involved in tissue-specific transcriptional regulation.