The purpose of this research program is to initiate the molecular analysis of the human gene encoding glucocerebrosidase, the enzyme which is deficient in patients with Gaucher's disease. Initially, we will construct a cDNA library from normal human cell mRNA in a prokaryote expression vector. A cDNA clone of glucocerebrosidase mRNA will be isolated from this library by immunologic screening of the cDNA library for synthesis of human glucocerebrosidase protein segments using a specific anti-glucocerebrosidase antibody. The human glucocerebrosidase cDNA clone will then be used as a molecular probe for the isolation and study of the structure, function and expression of glucocerebrosidase genes of normal and glucocerebrosidase-deficient individuals. Such studies may allow for the identification of the molecular basis of Gaucher's disease. In addition these studies should facilitate carrier detection and prenatal diagnosis of this condition using synthetic oligonucleotides and/or restriction endonuclease cleavage polymorphisms of the glucocerebrosidase locus to distinguish between normal and mutant alleles. Eventually, glucocerebrosidase recombinant clones could also prove useful for attempts at treatment of Gaucher's disease by gene replacement.
| Eisenstein, R S; Hoganson, G; Miller, R H et al. (1991) Altered phosphorylation state of branched-chain 2-oxo acid dehydrogenase in a branched-chain acyltransferase deficient human fibroblast cell line. J Inherit Metab Dis 14:37-44 |
| Rauth, S; Hoganson, G E; Davidson, R L (1990) Bromodeoxyuridine- and cyclic AMP-mediated regulation of tyrosinase in Syrian hamster melanoma cells. Somat Cell Mol Genet 16:583-92 |
| Hoganson, G E; Ledwitz-Rigby, F; Davidson, R L et al. (1989) Regulation of tyrosinase mRNA levels in mouse melanoma cell clones by melanocyte-stimulating hormone and cyclic AMP. Somat Cell Mol Genet 15:255-63 |
