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 [Galβl–4(Fucαl–3)GlcNAcβ1–6(Ga1β1–3)GalNAcβ1–3Galα1–4Ga1β1–4Glcβ1-Cer], and the core 2 structure of O-linked glycans of glycoproteins, GlcNAcβ1-6(Ga1β1–3)GalNAcα-Ser/Thr, in a kidney tubular cell-specific manner through the regulation of UDP-GlcNAc β-l,6-GlcNAc transferase (GNT). Regulation by the G8l5 gene occurs at the level of GNT mRNA and the recessive allele of G8l5 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 G8l5 was introduced into laboratory mouse strains by Asian wild-derived mice. Phylogenetic comparison of the 5' flanking region sequences between the recessive and dominant G8l5 alleles indicates that mutations to create a functional G8l5 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.