Interspecific genetic complementation analysis of human and sheep fibroblasts with beta-galactosidase deficiency

• Published in: Somatic cell and molecular genetics Vol. 15; no. 6; p. 525
• Main Authors: Ahern-Rindell, A J, Murnane, R D, Prieur, D J
• Format: Journal Article
• Language: English
• Published: United States 01.11.1989
• Subjects: Animals; beta-Galactosidase - deficiency; beta-Galactosidase - genetics; Cats; Cell Fusion; Cells, Cultured; Fibroblasts - enzymology; Fluorometry; Galactosidases - deficiency; Galactosides; Gangliosidoses - genetics; Genetic Complementation Test; Humans; Indoles; Metabolism, Inborn Errors - genetics; Mucolipidoses - genetics; Mucolipidoses - metabolism; Mucopolysaccharidosis IV - genetics; Sheep
• ISSN: 0740-7750
• DOI: 10.1007/BF01534913

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.