Interspecific genetic complementation analysis of human and sheep fibroblasts with beta-galactosidase deficiency.
Interspecific somatic cell hybrids were analyzed by genetic complementation to determine if a lysosomal storage disease in sheep associated with deficiencies of beta-galactosidase and alpha-neuraminidase was homologous with any of four beta-galactosidase-deficient human diseases. Fibroblasts from beta-galactosidase-deficient sheep, cats, and human patients were fused and assayed histochemically for beta-galactosidase, with 5-bromo-4-chloro-3-indolyl beta-D-galactoside. We observed complementation in heterokaryons consisting of fibroblasts from beta-galactosidase-deficient sheep and fibroblasts from patients with galactosialidosis or mucolipidosis type II, but no complementation in heterokaryons consisting of fibroblasts from beta-galactosidase-deficient sheep and fibroblasts from human or feline GM1 gangliosidosis (type I) or from human mucopolysaccharidosis type IVB fibroblasts. We conclude that the ovine disease is due to a mutation at the genetic locus homologous with that of GM1 gangliosidosis and mucopolysaccharidosis type IVB, suggesting that the primary defect in the ovine disease is a mutation of the beta-galactosidase structural gene.
Ahern-Rindell
A J
AJ
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040.
Murnane
R D
RD
Prieur
D J
DJ
D000818:Animals; D002415:Cats; D002459:Cell Fusion; D002478:Cells, Cultured; D005347:Fibroblasts / Q000201:enzymology*; D005470:Fluorometry; D005696:Galactosidases / Q000172:deficiency*; D005697:Galactosides; D005733:Gangliosidoses / Q000235:genetics; D005816:Genetic Complementation Test; D006801:Humans; D007211:Indoles; D008661:Metabolism, Inborn Errors / Q000235:genetics*; D009081:Mucolipidoses / Q000235:genetics / Q000378:metabolism; D009085:Mucopolysaccharidosis IV / Q000235:genetics; D012756:Sheep; D001616:beta-Galactosidase / Q000172:deficiency* / Q000235:genetics
D005697:Galactosides; D007211:Indoles; D005696:Galactosidases; D001616:beta-Galactosidase; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside