Bovine Plasma β-Mannosidase Activity and Its Potential use for β-Mannosidosis Carrier Detection

Abstract

Abstract. Plasma ß-mannosidase activities were determined for Salers cattle from 8 herds as an evaluation of this method for detection of ß-mannosidosis heterozygotes. Several biological factors, such as age, gender, herd, and risk of being a ß-mannosidosis carrier, were considered in this study. The mean enzyme activity for obligate heterozygotes (n = 8) was 55 U/ml (range = 43-65 U/ml), which was 59% of the mean enzyme activity for cattle that were low risk for being a carrier. These data indicate that bovine ß-mannosidosis is characterized by a gene dosage effect. The analytical and biological variation of plasma ß-mannosidase activity that was observed necessitates limiting the test to adult fullblood/purebred Salers cattle within a herd. Plasma ß-mannosidase analysis provides important information for intraherd selection of Salers cattle that are heterozygous for ß-mannosidosis. ß-mannosidosis is an autosomal recessive defect of glycoprotein catabolism that has been reported in goats, 11,18,19 human 5,6,7,21,28 and, most recently, Salers cattle [1][2][3]13,25 From birth, affected Salers calves are unable to rise and have a characteristic appearance consisting of a slightly domed head, slight protrusion of the lower jaw, narrow eye openings, and abundant purplish gums. Handling of these calves reveals skin that seems tightly adhered to the body. The calves cannot stand even with assistance, and during periods of sternal recumbency they make wide circular head movements often combined with bobbing movements. These combined uncontrolled movements usually propel the calf into lateral recumbency. Affected calves cannot seek their mother to nurse, and even if milk/colostrum is offered (via a bottle) they are unable to suckle effectively. The disease is rapidly fatal in newborn ruminants. 1,17 Human ß-mannosidosis is clinically heterogeneous. Mental retardation and deafness are the most characteristic features. 6,7,21,28 Birth of affected calves has been reported in at least 4 states in the United States as well as in Canada and New Zealand. The American Salers Association has estimated that of 20,000 calves born in 1990, approximately 10 calves were positively diagnosed as having ß-mannosidosis. However, a true estimation of the gene frequency is not possible because the disease has only recently been described, and it may be confused with hydrocephalus or bovine viral diarrhea infection. Furthermore, reporting of bovine ß-mannosidosis is voluntary and breeders may be reluctant to report these cases for economically important livestock.The biochemical hallmark of this neurovisceral storage disease is the absence of plasma ß-mannosidase activity. In caprine and bovine ß-mannosidosis, Manß1-4G1cNAc and Marßl-4G1cNAcßl-4G1cNAc as well as more complex oligosaccharides accumulate in tissues and urine. 1,17,19,20,[22][23][24] The Manßl-4G1cNAc disaccharide is the main uncatabolized substrate in humans. 6,7,21,28 The disease is clinically and biochemically quite different from α−mannosidosis that is described in Angus,...