Mannosidosis in aborted and stillborn Galloway calves

Borland, NA; Jerrett, IV; Embury, D. H.

doi:10.1136/vr.114.16.403

Cited by 16 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, in feline and bovine a-mannosidosis (Vandevelde et al, 1982;Borland et al, 1984;Embury and Jerrett, 1985;Cummings et al, 1988) and in caprine and bovine 13-mannosidosis (Healy et al, 1981;Jones and Dawson, 1981;Jolly et al, 1991), increased activities of most hydrolases measured have been reported in brain, liver, and/or kidney, but the previous studies have not focused on the CNS sufficiently to note differences, as reported here, in the response of the CNS and organs to metabolic perturbations.…”

Section: Discussionmentioning

confidence: 64%

Biochemical and histochemical analysis of lysosomal enzyme activities in caprine β-mannosidosis

Lovell

Kranich

Cavanagh

1994

Molecular and Chemical Neuropathology

View full text Add to dashboard Cite

Goats affected with beta-mannosidosis, an autosomal recessive disease of glycoprotein catabolism, have deficient tissue and plasma levels of the lysosomal enzyme beta-mannosidase. Pathological characteristics include cytoplasmic vacuolation in the nervous system and viscera, and myelin deficits that demonstrate regional variation. This study was designed to determine the correlation between beta-mannosidase activity in normal animals and the severity of lesions in affected goats, and to assess the regional changes in lysosomal enzyme activity in specific regions and cell types in affected animals. Although enzyme activity in normal organs (kidney, thyroid, brain) is correlated in general with the accumulation of uncatabolized substrate and with the extent of vacuolation, this correlation does not extend to assessment of specific regions of the central nervous system (CNS). In affected goats, the activities of alpha-mannosidase, alpha-fucosidase, and beta-hexosaminidase are elevated to a greater extent in all CNS regions than in organs. The results suggest cell-specific, organ-specific, and enzyme-specific regulation of changes in lysosomal enzyme activity in the presence of metabolic perturbations, such as deficiency of beta-mannosidase activity.

show abstract

Section: Discussionmentioning

confidence: 64%

Biochemical and histochemical analysis of lysosomal enzyme activities in caprine β-mannosidosis

Lovell

Kranich

Cavanagh

1994

Molecular and Chemical Neuropathology

View full text Add to dashboard Cite

show abstract

“…Furthermore, free oligosaccharides (5) are imported from the cytosol by a so-far-unknown mechanism for lysosomal degradation. Besides this well-known catabolic function of LAMAN, our findings demonstrate that LAMAN is involved in the trimming of N-glycans on native lysosomal proteins (6), so that LAMAN deficiency leads to a hypermannosylation of lysosomal proteins. We also observed microheterogeneity, since high-mannosetype glycans were detected in small amounts in cathepsin B from mice with ␣-mannosidosis.…”

Section: Discussionmentioning

confidence: 60%

“…Naturally occurring animal models for ␣-mannosidosis have been described for cats (8,55), cattle (6,24), and guinea pigs (12). The animal models have been the subjects of various studies dealing with neuropathological, behavioral, and therapeutic aspects of ␣-mannosidosis (3,13,38).…”

mentioning

confidence: 99%

Impaired Lysosomal Trimming of N-Linked Oligosaccharides Leads to Hyperglycosylation of Native Lysosomal Proteins in Mice with α-Mannosidosis

Damme

Morelle

Schmidt

et al. 2010

Molecular and Cellular Biology

View full text Add to dashboard Cite

␣-Mannosidosis is caused by the genetic defect of the lysosomal ␣-D-mannosidase (LAMAN), which is involved in the breakdown of free ␣-linked mannose-containing oligosaccharides originating from glycoproteins with N-linked glycans, and thus manifests itself in an extensive storage of mannose-containing oligosaccharides. Here we demonstrate in a model of mice with ␣-mannosidosis that native lysosomal proteins exhibit elongated N-linked oligosaccharides as shown by two-dimensional difference gel electrophoresis, deglycosylation assays, and mass spectrometry. The analysis of cathepsin B-derived oligosaccharides revealed a hypermannosylation of glycoproteins in mice with ␣-mannosidosis as indicated by the predominance of extended Man3GlcNAc2 oligosaccharides. Treatment with recombinant human ␣-mannosidase partially corrected the hyperglycosylation of lysosomal proteins in vivo and in vitro. These data clearly demonstrate that LAMAN is involved not only in the lysosomal catabolism of free oligosaccharides but also in the trimming of asparaginelinked oligosaccharides on native lysosomal proteins.The lysosomal ␣-D-mannosidase (LAMAN; EC 3.2.1.24) belongs to the group of at least seven lysosomal exoglycosidases which sequentially degrade oligosaccharides derived from glycoproteins (2, 31). These glycoproteins enter the lysosomal compartment by either endocytic pathways (extracellular and plasma membrane proteins) or autophagic processes (intracellular proteins). In addition, free oligosaccharides originating from lipid-linked oligosaccharides in the endoplasmic reticulum and from glycoproteins by the endoplasmic reticulumassociated protein degradation (ERAD) pathway are transported into the lysosome, where these oligosaccharides are subsequently degraded (9, 45). Inside the lysosome, the degradation of the glycoproteins is described as a bidirectional process in which on the one hand the polypeptide is hydrolyzed by a cohort of lysosomal endo-and exoproteases with partially overlapping specificities like cathepsins and other peptidases 40,52). On the other hand, the sugar moiety is stepwise hydrolyzed into its monosaccharides by exoglycosidases. The precise order of the bidirectional breakdown of glycoproteins is unclear, although assumptions can be made based on the analysis of the storage products of the different glycoproteinoses (31). Therefore, it is assumed that an efficient degradation of the oligosaccharide chain is highly dependent on the cleavage of the protein-oligosaccharide linkage by the glycosylasparaginase (2, 31). In contrast, the proteolysis of the polypeptide backbone is mainly unaffected by intact oligosaccharide structures on the glycoproteins (1).LAMAN has a broad substrate specificity, cleaving nonreducing terminal ␣1,2-, ␣1,3-, and ␣1,6-mannosyl linkages found in complex-type, hybrid-type, and high-mannose-type asparagine-linked glycans (30, 60). Additionally, a second lysosomal mannosidase (MAN2B2) specific for the core ␣1,6 branch was characterized and found to be dependent on the prior enzymati...

show abstract

“…Subsequently, the disease was diagnosed in Angus cattle in Europe and the United States, and in Galloway cattle in Australia. [4][5][6]12 After mass screening programmes carried out in Australia and New Zealand, the α-mannosidosis mutant gene prevalence is insignificant; consequently the disease is relatively rare. 13,14 The Argentine Angus Association (AAA), member of the World Angus Secretariat, requires their members to declare the existence of several genetic diseases, and since 1 October 2019, α-mannosidosis testing is compulsory.…”

Section: Discussionmentioning

confidence: 99%

Bovine autosomal recessive alpha‐mannosidosis in an Aberdeen Angus herd from Argentina

Morris,

Delgado,

Micheloud

et al. 2023

Vet Record Case Reports

View full text Add to dashboard Cite

An outbreak of α‐mannosidosis in a bovine herd from Buenos Aires province is reported. Postmortem examination, histology, lectin histochemistry and electron microscopy were performed on five calves born with nervous signs. Hair samples from dams and calves were genetically analysed. The α‐mannosidase gene including exon 7 was amplified and sequenced. At postmortem examination, no gross changes were evident. Histologically, cytoplasmic neuronal vacuolation in the brain and cerebellum of the five calves, staining moderately to intensively, with lectin histochemistry was evident. Ultrastructurally, vacuoles containing finely granulated material in the cytoplasm of neurons, myelin degeneration and axonal swelling were seen in the brain. Genetic analysis revealed a heterozygous carrier state for 961T→C transition in the exon 7 of α‐mannosidosis gene of four cows, and a recessive homozygous state for 961T→C transition in the same genes in the calves analysed. This highlights the importance of identifying and removing animals carrying the α‐mannosidosis mutated gene.

show abstract

Mannosidosis in aborted and stillborn Galloway calves

Cited by 16 publications

References 0 publications

Biochemical and histochemical analysis of lysosomal enzyme activities in caprine β-mannosidosis

Biochemical and histochemical analysis of lysosomal enzyme activities in caprine β-mannosidosis

Impaired Lysosomal Trimming of N-Linked Oligosaccharides Leads to Hyperglycosylation of Native Lysosomal Proteins in Mice with α-Mannosidosis

Bovine autosomal recessive alpha‐mannosidosis in an Aberdeen Angus herd from Argentina

Contact Info

Product

Resources

About