There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
alpha-Mannosidosis is a lysosomal storage disorder resulting from a functional deficiency
of the lysosomal enzyme alpha-mannosidase. This deficiency results in the accumulation
of various oligosaccharides in the lysosomes of affected individuals, causing somatic
pathology and progressive neurological degeneration that results in cognitive deficits,
ataxia, and other neurological symptoms. We have a naturally occurring guinea pig
model of this disease which exhibits a deficiency of lysosomal alpha-mannosidase and
has a similar clinical presentation to human alpha-mannosidosis. Various tests were
developed in the present study to characterise and quantitate the loss of neurological
function in alpha-mannosidosis guinea pigs and to follow closely the progression of
the disease. General neurological examinations showed progressive differences in alpha-mannosidosis
animals from approximately 1 month of age. Significant differences were observed in
hind limb gait width from 2 months of age and significant cognitive (memory and learning)
deficits were observed from 3 months of age. Evoked response tests showed an increase
in somatosensory P1 peak latency in alpha-mannosidosis guinea pigs from approximately
2 months of age, as well as progressive hearing loss using auditory brainstem evoked
responses. The alpha-mannosidosis guinea pig therefore appears to exhibit many of
the characteristics of the human disease, and will be useful in evaluating therapies
for treatment of central nervous system pathology.