Arylsulfatase A-deficient mice - A model for studying metachromatic leukodystroph
Ref.-Nr. 3206_4908
Keywords: Mausmodell, Knockout-Maus, transgene Maus, Arylsulfatase A-Defizienz, Metachromatische Leukodystrophie, lysosomale Speicherkrankheit, mouse model, knockout mice, transgenic mice, Arylsulfatase A deficiency, metachromatic leukodystrophy, lysosomal storage disorder
This results in accumulation of sulfated glycosphingolipids, mainly 3-O-sulfogalactosylceramide (sulfatide), in the nervous system and various other organs. In patients, lipid storage causes a progressive loss of myelin leading to various neurological symptoms. The sulfatide storage in ASA-deficient mice is comparable to humans, but the mice do not mimic the myelin pathology. Therefore, in addition to the sole transgenic ASA-deficient (tg/ASA(-/-)) knock-out mice, a second model was generated further overexpressing the sulfatide-synthesizing enzyme galactose-3-O-sulfotransferase. These mice displayed a significant increase in sulfatide storage in the brain and peripheral nerves. Mice older than one year developed severe neurological symptoms. Nerve conduction velocity was significantly reduced due to hypomyelinated and demyelinated axons of the nerves. Thus, increasing sulfatide storage in ASA-deficient mice leads to neurological symptoms and morphological alterations that are reminiscent of human MLD.
Vorteile
- Mouse models with
- sulfatide storage
- neuropathy
- neurological symptoms
- Valuable model for metachromatic leukodystrophy
- Matching models of symptomatic and asymptomatic mice
Aktueller Stand
On behalf of the University Bonn, PROvendis offers access to both the sole transgenic ASA-deficient (tg/ASA(-/-)) knock-out mouse model and the ASA-deficient (tg/ASA(-/-)) knock-out mouse model overexpressing the sulfatide-synthesizing enzyme galactose-3-O-sulfotransferase under a Material License Agreement. The two models are available in combination or separately.
Relevante Veröffentlichungen
Hess, B., et al. (1996) Phenotype of arylsulfatase A-deficient mice: Relationship to human metachromatic leukodystrophy. Proc. Natl. Acad. Sci. USA 93: 14821-6.
Ramakrishnan, H., et al. (2007) Increasing sulfatide synthesis in myelin-forming cells of arylsulfatase A-deficient mice causes demyelination and neurological symptoms reminiscent of human metachromatic leukodystrophy, J. Neurosci, 27(35): 9482-90.
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Eine Erfindung der Uni Bonn.
