The UDP-galactose-4-epimerase (GALE) catalyzes the interconversion of UDP-galactose (UDP-Gal) and UDP-glucosa (UDP-Glc) as well as the interconversion of UDP-N-acetlygalactosamine (UDP-GalNAc) and UDP-N-acetylglucosamine (UDP-GlcNAc). Therefore, this enzyme participates in the generation of different UDP sugars species needed for the synthesis of glyproteins glycolipids, proteoglycans and glucosoaminoglycans, which have an essential role in different function like development or immune response (Mumma et al. 2008). We have isolated the mutant
gale-1(
pv18) which is a hypomorphic allele of the UDP-galactose-4-epimerase which shows an altered level of those UDP-sugars named before, especially UDP-N-acetlygalactosamine which is largely reduced. When this mutant develops at 25C animals die as embryos, but at lower temperatures develop to fertile adult. Those animals show several developmental abnormalities, among them gonad and vulva misshaped. The gonad abnormalities are similar to the one described for the
mig-17 mutant. Mig-17 encodes to a methaloprotease that need to be glycosylated for its right location and function. We have observed that in a
gale-1 mutant background
mig-17 is misslocalized indicating that
mig-17 is affected by the changes in the level of UDP-sugars and provide an explanation for at least the gonad misshaped phenotype. Mutation in the human
gale-1 homologue gene results in an autosomal recessive disorder known as type III galactosemia. We are now trying to complement the C. elegans mutant with the human GALE cDNA, and studying the possibility to use the C.elegans
gale-1 mutant as a model for this rare disorder.