In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 93, No. 25 ( 1996-12-10), p. 14821-14826
Abstract:
Metachromatic leukodystrophy is a lysosomal sphingolipid storage
disorder caused by the deficiency of arylsulfatase A. The disease is characterized by progressive demyelination, causing various neurologic
symptoms. Since no naturally occurring animal model of the disease is available, we have generated arylsulfatase A-deficient mice. Deficient
animals store the sphingolipid cerebroside-3-sulfate in various neuronal and nonneuronal tissues. The storage pattern is comparable to
that of affected humans, but gross defects of white matter were not observed up to the age of 2 years. A reduction of axonal
cross-sectional area and an astrogliosis were observed in 1-year-old mice; activation of microglia started at 1 year and was generalized at
2 years. Purkinje cell dendrites show an altered morphology. In the acoustic ganglion numbers of neurons and myelinated fibers are severely
decreased, which is accompanied by a loss of brainstem auditory-evoked potentials. Neurologic examination reveals significant
impairment of neuromotor coordination.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.93.25.14821
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1996
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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