title: Behavioural characterisation of the alpha-mannosidosis guinea pig.
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.
authors: Lysosomal Diseases Research Unit, Department of Genetic Medicine, Children, Youth and Women's Health Service,72 King William Road, North Adelaide, South Australia, Australia.
authors: A J
authors: AJ
authors: Robinson
authors: A C
authors: AC
authors: Crawley
authors: D
authors: D
authors: Auclair
authors: P F
authors: PF
authors: Weston
authors: C
authors: C
authors: Hirte
authors: K M
authors: KM
authors: Hemsley
authors: J J
authors: JJ
authors: Hopwood
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D005684:Gait / Q000502:physiology; D006168:Guinea Pigs; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009460:Neurologic Examination; D011930:Reaction Time; D012737:Sex Factors; D043323:alpha-Mannosidase / Q000172:deficiency; D008363:alpha-Mannosidosis / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology*
chemical_list: D043323:alpha-Mannosidase