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

Abstract

Interspecific somatic cell hybrids were analyzed by genetic complementation to determine if a lysosomal storage disease in sheep associated with deficiencies of β-galactosidase and α-neuraminidase was homologous with any of four β-galactosidase-deficient human diseases. Fibroblasts from β-glactosidase-deficient sheep, cats, and human patients were fused and assayed histochemically for β-galactosidase, with 5-bromo-4-chloro-3-indolyl β-d-galactoside. We observed complementation in heterokaryons consisting of fibroblasts from β-galactosidase-deficient sheep and fibroblasts from patients with galactosialidosis or mucolipidosis type II, but no complementation in heterokaryons consisting of fibroblasts from β-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 β-galactosidase structural gene. © 1989 Plenum Publishing Corporation.