Cloning and characterization of cDNAs encoding a candidate glycogen storage disease type 1b protein in rodents

Glycogen storage disease type 1 (GSD-I) is a group of genetic disorders caused by a deficiency in the activity of the enzyme glucose-6-phosphatase. (G6Pase). GSD-la and GSD-lb, the two major subgroups, have been confirmed at the molecular genetic level. The gene responsible for GSD-lb maps to human chromosome 11q23 and a candidate human GSD-lb cDNA that encodes a microsomal transmembrane protein has been identified. In this study, we show that this cDNA maps to chromosome 11q23; thus it is a strong candidate for GSD-lb. Furthermore, we isolated and characterized candidate murine and rat GSD-lb cDNAs. Both encode transmembrane proteins sharing 93-95% sequence homology to the human GSD-lb protein. The expression profiles of murine GSD-lb and G6Pase differ both in the liver and in the kidney; the GSD-lb transcript appears before the G6Pase mRNA during development. In addition to G6Pase deficiency, GSD-lb patients suffer neutropenia, neutrophil dysfunction, and recurrent bacterial infections. Interestingly, although the G6Pase mRNA is expressed primarily in the liver, kidney, and intestine, the GSD-lb mRNA is expressed in numerous tissues, including human neutrophils/monocytes.