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 disorder s caused by a deficiency in the activity of the enzyme glucose-6-phosp hatase. (G6Pase). GSD-la and GSD-lb, the two major subgroups, have bee n confirmed at the molecular genetic level. The gene responsible for G SD-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 i t is a strong candidate for GSD-lb. Furthermore, we isolated and chara cterized candidate murine and rat GSD-lb cDNAs. Both encode transmembr ane proteins sharing 93-95% sequence homology to the human GSD-lb prot ein. The expression profiles of murine GSD-lb and G6Pase differ both i n the liver and in the kidney; the GSD-lb transcript appears before th e G6Pase mRNA during development. In addition to G6Pase deficiency, GS D-lb patients suffer neutropenia, neutrophil dysfunction, and recurren t bacterial infections. Interestingly, although the G6Pase mRNA is exp ressed primarily in the liver, kidney, and intestine, the GSD-lb mRNA is expressed in numerous tissues, including human neutrophils/monocyte s.