Mannosidosis in Angus cattle. The enzymic defect

Area of Science:

• Biochemistry
• Veterinary Medicine
• Genetics

Background:

• Alpha-mannosidase is a crucial enzyme involved in glycoprotein metabolism.
• Deficiency in lysosomal alpha-mannosidase activity leads to mannosidosis, a lysosomal storage disorder.
• Previous studies indicated genetic defects in alpha-mannosidase in affected cattle breeds.

Purpose of the Study:

• To characterize the different forms of alpha-mannosidase in normal and mannosidotic calf tissues and plasma.
• To investigate the specific alpha-mannosidase deficiency underlying Angus-cattle mannosidosis.
• To support the hypothesis of a lysosomal storage disease caused by deficient acidic alpha-mannosidase.

Main Methods:

• Separation of alpha-mannosidase forms using DEAE-cellulose chromatography and starch-gel electrophoresis.
• Enzyme activity assays across a range of pH values.
• Analysis of molecular weight and sensitivity to metal ions (EDTA, Zn2+, Co2+, Mn2+).
• Comparison of enzyme profiles in normal versus mannosidotic calf tissues and plasma.

Main Results:

• Normal calf tissues exhibit at least three alpha-mannosidase forms (A, B, C) with distinct pH optima.
• Components A and B (acidic optima) are absent in mannosidotic calf tissues, with residual activity attributed to component C (neutral optimum).
• Normal plasma contains an acidic alpha-mannosidase (pH optimum 4.0) absent in mannosidotic calf plasma, where residual activity has a pH optimum of 5.5-5.75.

Conclusions:

• Angus-cattle mannosidosis is characterized by a deficiency in lysosomal acidic alpha-mannosidase.
• The observed differences in enzyme properties (pH optimum, molecular weight, ion sensitivity) distinguish acidic and neutral forms.
• The findings strongly support the hypothesis that mannosidosis in this breed is a storage disease resulting from a specific enzyme defect.