Globoid cell leukodystrophy (Krabbe disease) is an autosomal recessive disorder 
resulting from the deficiency of galactocerebrosidase (GALC) activity. GALC is 
responsible for the lysosomal catabolism of galactosylceramide, a major lipid in 
myelin, kidney and epithelial cells of small intestine and colon. We describe 
the molecular cloning of human GALC cDNA and its expression in COS-1 cells. 
Degenerate PCR primers, derived from N-terminal amino acid sequence from the 51 
kDa band from human brain, were used to amplify cat testes RNA, and the 
resulting product was used to screen human testes and brain libraries. Two 
overlapping clones contained the total protein coding region, while additional 
clones and PCR amplification were needed to obtain the complete 3' end of the 
cDNA. The 3795 bp obtained include 47 bp 5' to the initiation start site, 2007 
bp of open reading frame (coding for 669 amino acids), and 1741 bp of 3' 
untranslated sequence. Modification of the sequence surrounding the initiation 
codon to one more favorable for expression, resulted in a 6-fold increase in 
GALC activity in transfected COS-1 cells. The isolation of this clone will 
permit investigations into the causes for GALC deficiency in humans and 
available animal models, development of more accurate tests for patient and 
carrier identification, and evaluation of methods for effectively treating GALC 
deficiency, initially using the animal models.