Abstract

Prospective and retrospective genetic studies were performed on sheep with a recently described inherited lysosomal storage disease that involves a profound deficiency of beta-galactosidase and an associated deficiency of alpha-neuraminidase. Retrospective studies of the flock of sheep in which four affected lambs were born indicated little inbreeding but the presence of a common ram in both the maternal and paternal sides of the pedigrees. When unrelated rams were used in the flock in subsequent years, no affected lambs were born. The affected lambs' parents were phenotypically normal, so the disease was investigated as a putative autosomal recessive condition in prospective breedings of related sheep over two breeding seasons. For the third breeding season, heterozygous ewes were superovulated and bred to a heterozygous ram, and the resultant embryos were transferred to recipient ewes. Later in the same breeding season, the heterozygous ewes were re-bred naturally to the heterozygous ram. Lambs were identified as affected by the development of signs of ataxia, levels of beta-galactosidase that were less than 7% of the levels in controls by spectrofluorometric assay, or the histopathologic demonstration of vacuolization of neurons. Heterozygous sheep were identified by the production of affected offspring and/or by levels of beta-galactosidase in fibroblast cultures that were approximately 50% of control levels. The phenotypic ratio of affected sheep to normal sheep and the genotypic ratio of affected to heterozygous to normal sheep were consistent, by chi-square analysis, with an autosomal recessive trait. It was concluded that this ovine lysosomal storage disease is an autosomal recessive disease.