Lesch-Nyhan disease is caused by a deficiency of the
purine salvage
enzyme,
hypoxanthine phosphoribosyl
transferase (
HPRT). The link between
HPRT deficiency and the neuropsychiatric symptoms is unknown. In rat B103
neuroblastoma cell membranes and mouse Neuro2a
neuroblastoma cell membranes,
nucleoside 5'-triphosphatase (
NTPase) activity is substantially reduced, whereas in fibroblast membranes from
HPRT knock-out mice,
NTPase activity is increased. Candidate genes for these
NTPase activity changes are ecto-
nucleoside 5'-triphosphate diphosphohydrolases (NTPDases). Therefore, we studied expression of NTPDases in B103 cells, Neuro2a cells and skin fibroblasts by
reverse transcriptase polymerase chain reaction and restriction
enzyme digestion of amplified
cDNA fragments. In B103 cells, expression of NTPDases 1, 3 and 6 decreased, whereas expression of NTPDases 4 and 5 increased in
HPRT deficiency. In Neuro2a cells, expression of NTPDases 3-6 increased in
HPRT deficiency. In fibroblasts,
NTPDase 3 expression decreased, and expression of NTPDases 4-6 increased in
HPRT deficiency. Collectively, there are complex decreases and increases in NTPDase
isoform expression in
HPRT deficiency that depend on the specific cell type and species studied. These changes in NTPDase expression may reflect an (insufficient) attempt of cells to compensate for the changes in
nucleotide metabolism caused by
HPRT deficiency.