title: Morphopathological features in tissues of alpha-mannosidosis guinea pigs at different gestational ages.
abstract: Alpha-mannosidosis is an inherited metabolic disorder characterized by a reduction in alpha-D-mannosidase and intralysosomal accumulation of undegraded mannose-containing oligosaccharides. The alpha-mannosidosis guinea pig exhibits pathological similarities to its human counterpart, which make it a valuable animal model. To trace the progression of alpha-mannosidosis during foetal development, brain and visceral organs from affected and unaffected guinea pigs at 30, 36, 38, 51 and 65 days of gestation (dg) were examined by light and electron microscopy (term: approximately 68 dg). In the affected brain, distended lysosomes (vacuoles) were scarce up to 38 dg and were seen in few differentiating neuronal cells but mostly in macrophages, pericytes and endothelial cells. At 51 and 65 dg, several vacuoles were observed in some neurones, in many Purkinje cells, pericytes, endothelial and microglial cells, and in few cerebellar internal granule cells. Myelination had started by 51 dg. Non-myelinated axonal spheroids were detected in the brainstem at 65 dg. In the kidney cortex and liver, an increase in vacuolation was noticed between 36 and 65 dg. Some vacuolated cells were also noticed in the lungs and spleen at 51 and 65 dg. Altogether, these histological observations suggest that alpha-mannosidosis is unlikely to affect ontogenesis before the second half of gestation in guinea pigs; however, the morphopathological features recorded during the last quarter of gestation (which may roughly correspond to the period covering near term to 1-2 years of age in human) were clearly noticeable and may have had some impact.
authors.affiliation: Lysosomal Diseases Research Unit, Department of Genetic Medicine, Children, Youth and Women's Health Service, North Adelaide, South Australia, Australia. dyane.auclair@adelaide.edu.au
authors.forename: D
authors.initials: D
authors.lastname: Auclair
authors.forename: J J
authors.initials: JJ
authors.lastname: Hopwood
mesh_terms: D000818:Animals; D001921:Brain / Q000648:ultrastructure*; D018450:Disease Progression; D005260:Female; D005333:Fetus / Q000473:pathology*; D006168:Guinea Pigs; D046529:Microscopy, Electron, Transmission; D011247:Pregnancy; D014781:Viscera / Q000473:pathology*; D008363:alpha-Mannosidosis / Q000473:pathology*