Modest phenotypic improvements in ASA-deficient mice with only one UDP-galactose:ceramide-galactosyltransferase gene

• Published in: Lipids in health and disease 2006-08, Vol.5 (1), p.21-21
• Main Authors: Franken, S, Wittke, D, Mansson, J E, D'Hooge, R, De Deyn, P P, Lüllmann-Rauch, R, Matzner, U, Gieselmann, V
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Behavior, Animal - physiology; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Brain - metabolism; Brain - pathology; Breeding; Cerebroside-Sulfatase - deficiency; Cerebroside-Sulfatase - genetics; Cerebroside-Sulfatase - metabolism; Disease Models, Animal; Ear, Inner - metabolism; Ear, Inner - pathology; enzyme replacement therapy; Female; Galactosylceramides - metabolism; Genotype; Leukodystrophy, Metachromatic - genetics; Leukodystrophy, Metachromatic - pathology; Leukodystrophy, Metachromatic - physiopathology; lysosomal storage diseases; Male; metachromatic leukodystrophy; Mice; Mice, Knockout; Motor Activity - physiology; mouse model; N-Acylsphingosine Galactosyltransferase - genetics; N-Acylsphingosine Galactosyltransferase - metabolism; n-butyldeoxynojirimycin; nervous-system; Neurons - metabolism; Neurons - pathology; Phenotype; substrate reduction therapy; sulfatide storage; Sulfoglycosphingolipids - metabolism; Time Factors; transgenic mice; type-1 gaucher-disease; Uridine Diphosphate Galactose - metabolism
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/1476-511X-5-21

Arylsulfatase A (ASA)-deficient mice are a model for the lysosomal storage disorder metachromatic leukodystrophy. This lipidosis is characterised by the lysosomal accumulation of the sphingolipid sulfatide. Storage of this lipid is associated with progressive demyelination. We have mated ASA-deficient mice with mice heterozygous for a non-functional allele of UDP-galactose:ceramide-galactosyltransferase (CGT). This deficiency is known to lead to a decreased synthesis of galactosylceramide and sulfatide, which should reduce sulfatide storage and improve pathology in ASA-deficient mice. ASA-/- CGT+/- mice, however, showed no detectable decrease in sulfatide storage. Neuronal degeneration of cells in the spiral ganglion of the inner ear, however, was decreased. Behavioural tests showed small but clear improvements of the phenotype in ASA-/- CGT+/- mice. Thus the reduction of galactosylceramide and sulfatide biosynthesis by genetic means overall causes modest improvements of pathology.