International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 109 - PHYLOGENETIC DEVELOPMENT OF A REGULATORY GENE FOR THE CORE2 GLCNAC TRANSFERASE IN MUS MUSCULUS

M Sekine
The Tokyo Metropolitan Institute of Medical Science

1) Kikkawa Y, 1) Taya C, 2) Suzuki A, 1) Yonekawa H
1) The Tokyo Metropolitan Institute of Medical Science, 2) RIKEN Frontier Research System

We have identified a mouse gene, Gsl5, which controls the expression of a glycolipid, GL-Y [Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Galbeta1-3)GalNAcbeta1-3Galalpha1-4Galbeta1-4Glcbeta1-Cer] and the core2 structure of O-linked glycans of glycoproteins, GlcNAcbeta1-6(Galbeta1-3)GalNAcalpha-Ser/Thr, in a kidney tubular cell-specific manner. The Gsl5 regulates the transcription of UDP-GlcNAc beta-1,6-GlcNAc transferase (c2GnT) and was mapped to chromosome 19, closely linked to c2GnT gene. An inbred strain, DBA/2, which cannot express GL-Y, has a recessive allele of Gsl5. The DBA/2 phenotype is rare in the laboratory strains but found in all of mice which are derived from a M.m.musculus subspecies distributed from East Europe to Far East Asia. A sequence comparison for the 5 flanking region of the c2GnT gene among 5 laboratory strains and 10 wild-derived strains suggests that DBA/2 allele of Gsl5 was introduced into laboratory mouse strains by Asian wild-derived mice. BAC-rescue experiment using a 150 kb clone that contains c2GnT gene, suggests that Gsl5 is included in the same clone. We have sequenced its 40 kb fragment including the exon1 and intron1 of c2GnT gene, and compared it with the corresponding region of DBA/2 genomic DNA. DBA/2 genomic sequence shows 8 deletions, 5 insertions and a lot of single nucleotide polymorphisms (SNPs). We are now trying to make DNA constructs for the promoter/enhancer assay to elucidate what Gsl5 encodes.


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