Research

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

S Franken^1,6 , D Wittke² , JE Mansson³ , R D'Hooge⁴ , PP De Deyn⁵ , R Lüllmann-Rauch² , U Matzner¹ and V Gieselmann¹

¹Department of Physiological Chemistry, University of Bonn, Germany

²Anatomisches Institut, Universität Kiel, Germany

³Institute of Clinical Neuroscience, Goteborg University, Sweden

⁴Laboratory of Biological Psychology, University of Leuven, Belgium

⁵Department of Biomedical Sciences and Department of Neurology/Memory Clinic, University of Antwerp, Belgium

⁶Institut für Physiologische Chemie, Rheinische-Friedrich-Wilhelms Universität, Nussallee 11, 53115, Bonn, Germany

author email corresponding author email

Lipids in Health and Disease 2006, 5:21doi:10.1186/1476-511X-5-21

Published:	7 August 2006

Abstract

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.

Conclusion

Thus the reduction of galactosylceramide and sulfatide biosynthesis by genetic means overall causes modest improvements of pathology.