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Neurophysiological, behavioral and morphological abnormalities in the Fabry knockout mice.
- Source :
-
Neurobiology of disease [Neurobiol Dis] 2009 Jan; Vol. 33 (1), pp. 48-56. Date of Electronic Publication: 2008 Sep 23. - Publication Year :
- 2009
-
Abstract
- Fabry disease (OMIM 301500) is a rare X-linked recessive disorder caused by mutations in the alpha-galactosidase gene (GLA). Loss of alpha-galactosidase (alpha-Gal) activity leads to the abnormal accumulation of glycosphingolipids in lysosomes predominantly of vascular endothelial cells. Clinically the disorder presents with angiokeratomas, clouding of the cornea, and renal, cardiac, and cerebrovascular complications. In addition, there is an increased incidence of neuropathic pain in Fabry patients. In this study, we investigated the implications of loss of alpha-galactosidase A activity on sensorimotor function and peripheral nervous system. Similar to the described in Fabry disease patients, the sensorimotor assessment of Fabry mice revealed diminished locomotor activity and warm hypoalgesia as assessed in the hot-plate. Moreover Fabry mice displayed alterations both in balance and co-ordination. By histological analysis, the cyto-architecture of Fabry mice sciatic nerves showed an increase in mean cross-sectional area accompanied by a decrease in the density of non-myelinated fibers as well as a trend for a decreased number of small myelinated fibers, a well established feature of Fabry disease. A relative preservation of large myelinated fibers and nerve conduction velocity measurements was observed. Our findings demonstrate for the first time that Fabry knockout mice have Gb3 accumulation in the peripheral nervous system, alterations in sensorimotor function, hypoalgesia and no impairment of motor nerve conduction.
- Subjects :
- Animals
Ataxia physiopathology
Disease Models, Animal
Female
Glycosphingolipids metabolism
Hot Temperature
Hypesthesia physiopathology
Male
Mice
Mice, Knockout
Motor Activity
Nerve Fibers pathology
Nerve Fibers physiology
Nerve Fibers ultrastructure
Neural Conduction physiology
Pain physiopathology
Peripheral Nervous System ultrastructure
Phenotype
Postural Balance
Sciatic Nerve pathology
Sciatic Nerve physiopathology
Sciatic Nerve ultrastructure
Thermosensing
Trihexosylceramides metabolism
alpha-Galactosidase metabolism
Fabry Disease pathology
Fabry Disease physiopathology
Fabry Disease psychology
Peripheral Nervous System pathology
Peripheral Nervous System physiopathology
alpha-Galactosidase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1095-953X
- Volume :
- 33
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neurobiology of disease
- Publication Type :
- Academic Journal
- Accession number :
- 18848893
- Full Text :
- https://doi.org/10.1016/j.nbd.2008.09.001