title: Evidence of a progressive motor dysfunction in Mucopolysaccharidosis type I mice.
abstract: Mucopolysaccharidosis (MPS) type I (Hurler syndrome) is a lysosomal storage disorder characterized by deficiency of alpha-L-iduronidase (IDUA), intracellular storage of glycosaminoglycans (GAGs) and progressive neurological pathology. The MPS I mouse model provides an opportunity to study the pathophysiology of this disorder and to determine the efficacy of novel therapies. Previous work has demonstrated a series of abnormalities in MPS I mice behavior, but so far some important brain functions have not been addressed. Therefore, in the present study we aimed to determine if MPS I mice have motor abnormalities, and at what age they become detectable. MPS I and normal male mice from 2 to 8 months of age were tested in open-field for locomotor activity, hindlimb gait analysis and hang wire performance. We were able to detect a progressive reduction in the crossings and rearings in the open field test and in the hang wire test in MPS I mice from 4 months, as well as a reduction in the gait length at 8 months. Histological examination of 8-month old mice cortex and cerebellum revealed storage of GAGs in Purkinje cells and neuroinflammation, evidenced by GFAP immunostaining. However TUNEL staining was negative, suggesting that death does not occur. Our findings suggest that MPS I mice have a progressive motor dysfunction, which is not caused by loss of neuron cells but might be related to a neuroinflammatory process.
authors.affiliation: Gene Therapy Center - Research Center - Hospital de Clinicas de Porto Alegre, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Baldo
authors.forename: Fabiana Quoos
authors.initials: FQ
authors.lastname: Mayer
authors.forename: Barbara
authors.initials: B
authors.lastname: Martinelli
authors.forename: Anna
authors.initials: A
authors.lastname: Dilda
authors.forename: Fabiola
authors.initials: F
authors.lastname: Meyer
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Ponder
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Ursula
authors.initials: U
authors.lastname: Matte
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005684:Gait / Q000235:genetics / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006025:Glycosaminoglycans / Q000652:urine; D018737:Hand Strength / Q000502:physiology; D007068:Iduronidase / Q000172:deficiency; D020287:In Situ Nick-End Labeling; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009069:Movement Disorders / Q000209:etiology* / Q000235:genetics; D008059:Mucopolysaccharidosis I / Q000150:complications* / Q000235:genetics* / Q000652:urine
chemical_list: D005904:Glial Fibrillary Acidic Protein; D006025:Glycosaminoglycans; D007068:Iduronidase