title: Development of motor deficits in a murine model of mucopolysaccharidosis type IIIA (MPS-IIIA).
abstract: Mucopolysaccharidosis (MPS) type IIIA or Sanfilippo syndrome is a lysosomal storage disorder characterised by progressive neurological pathology. Patients exhibit aggression, disturbed sleep, hyperactivity and mental decline ultimately resulting in inanition and death. Recently, a mouse model of MPS-IIIA was discovered, and both the clinical signs and neuropathological changes mimic the human disease. This provides us with an opportunity to study the pathological progression of this disorder and to determine the efficacy of novel therapies, for at present all lysosomal storage disorders (LSD) affecting the brain are untreatable. Neuropathological changes have previously been described in areas of the brain involved in regulating motor function, therefore, in the present study we sought to determine whether quantifiable motor abnormalities were present in the MPS-IIIA mouse, and if so, at what age they became detectable. Tests of open-field locomotor activity, hindlimb gait, catalepsy, neuromuscular strength and negative geotaxis were administered to MPS-IIIA and normal male and female mice aged from 3 to 40 weeks of age. Significant changes in open-field activity were observed from 3 weeks in MPS-IIIA mice, whereas abnormalities in tests of gait, grip strength and in the assessment of the negative geotaxis response were observable from approximately 15 weeks of age. Behavioural changes were often detected in male MPS-IIIA mice before they appeared in females. Our observations provide insight into the chronology of pathological changes within the MPS-IIIA brain and this simple series of tests will prove useful in comparing mice following the administration of experimental therapies for this condition.
authors.affiliation: Lysosomal Diseases Research Unit, Department of Genetic Medicine, Women's and Children's Hospital, 72 King William Road, North Adelaide, SA 5006, Australia. kim.hemsley@adelaide.edu.au
authors.forename: Kim M
authors.initials: KM
authors.lastname: Hemsley
authors.forename: John J
authors.initials: JJ
authors.lastname: Hopwood
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002375:Catalepsy / Q000503:physiopathology; D005260:Female; D005684:Gait / Q000502:physiology; D005838:Genotype; D018737:Hand Strength / Q000502:physiology; D016464:Lysosomal Storage Diseases / Q000503:physiopathology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009069:Movement Disorders / Q000209:etiology / Q000503:physiopathology*; D009084:Mucopolysaccharidosis III / Q000150:complications / Q000503:physiopathology*; D004856:Postural Balance