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


RESULTS
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.


CONCLUSIONS
Thus the reduction of galactosylceramide and sulfatide biosynthesis by genetic means overall causes modest improvements of pathology.
Franken
S
S
Department of Physiological Chemistry, University of Bonn, Germany. franken@institut.physiochem.uni-bonn.de
Wittke
D
D
Mansson
J E
JE
D'Hooge
R
R
De Deyn
P P
PP
Lüllmann-Rauch
R
R
Matzner
U
U
Gieselmann
V
V
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001947:Breeding; D002553:Cerebroside-Sulfatase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000378:metabolism / Q000473:pathology; D005260:Female; D005699:Galactosylceramides / Q000378:metabolism; D005838:Genotype; D007966:Leukodystrophy, Metachromatic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D051146:N-Acylsphingosine Galactosyltransferase / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D013433:Sulfoglycosphingolipids / Q000378:metabolism; D013997:Time Factors; D014531:Uridine Diphosphate Galactose / Q000378:metabolism*
D005699:Galactosylceramides; D013433:Sulfoglycosphingolipids; D014531:Uridine Diphosphate Galactose; D051146:N-Acylsphingosine Galactosyltransferase; D002553:Cerebroside-Sulfatase