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|Antigen/Gene or Protein Targets||Arylsulfatase A (ASA)-deficient|
|Disease Keywords||Metachromatic leukodystophy (MLD)|
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulfatase A (ASA). 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, transgenic ASA-deficient (tg/ASA(-/-)) mice were generated overexpressing the sulfatide-synthesizing enzyme galactose-3-O-sulfotransferase. These tg/ASA(-/-) mice displayed a significant increase in sulfatide storage in the brain and peripheral nerves. Mice older than 1 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.
|Growth/Phenotype Keywords||Older tg/ASA(-/-) mice, develop severe behavioural abnormalities due to progressive hindlimb paralysis|
|Mouse Genetic Background/Cross History||Two (female) tg founder mice (tg2639 and tg2645) were bred with ASA(-/-) mice (129/Ola background).|
|Research Area||Cell Structure and Motility, Genetic Studies Tools, Neurobiology, Protein Degradation|
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