Log in Register
Menu

Arylsulfatase A-deficient Mouse

Info

Antigen/Gene or Protein Targets Arylsulfatase A (ASA)-deficient
Disease Keywords Metachromatic leukodystophy (MLD)
Relevance 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.
Conditional No
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

References: 1 entry

Ramakrishnan et al. 2007. J Neurosci. 27(35):9482-90. PMID: 17728461.


Add a reference

References: 1 entry

Ramakrishnan et al. 2007. J Neurosci. 27(35):9482-90. PMID: 17728461.


Add a reference

References: 1 entry

Ramakrishnan et al. 2007. J Neurosci. 27(35):9482-90. PMID: 17728461.


Add a reference


This reagent does not have any reviews at the moment.