Journal of Inherited Metabolic Disease vol:23 suppl 1 pages:222-222
VIIIth International Congress of Inborn Errors of Metabolism edition:8 location:Cambridge - UK date:13-17 Sptember 2000
Transgenic mice de¢cient in arylsulfatase A (ASA) were generated as a putative model for the neurodegenerative lipidosis metachromatic leukodystrophy. ASA(-/-) and wildtype control mice were tested between 3 months and 2 years of age using a battery of behavioural tasks. It was found that ASA(-/-) mice display age-related impairments on several tests of neuromotor function and activity as well as on tests of learning and memory. One-year-old ASA(-/-) mice showed impaired rotarod
performance and walking with a shorter pace, later evolving into more severe ataxia with tremor in 2- year-old animals. These late defects might be related to selective neurodegeneration within the cerebellum of these ageing animals. However, performance of ASA(-/-) mice on tests of learning and memory also showed de¢cits which could not be reduced to neuromotor impairment. Whereas passive avoidance learning was not impaired in 3- and 6-month-old ASA(-/-) mice, 12-month-old animals did show signi¢cantly impaired passive avoidance retention. Acquisition and probe (retention) trial performance in the Morris water maze test of spatial learning and memory was normal in 3-month-old ASA(-/-) mice; slight impairments were seen in 6-month-old animals; whereas 12-month-old animals displayed markedly impaired acquisition and retention performance indicative of more profound cognitive impairment in these older animals.