Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulphatase A (ASA). This leads to the accumulation of the sphingolipid 3‐O‐sulphogalactosylceramide (sulphatide) and progressive demyelination in the nervous system of MLD patients. The mechanisms and development of pathology in the disease are still largely unknown. In this study we investigate how the inability to degrade sulphatide affects the formation of myelin in ASA‐deficient (ASA<jats:sup>–/–</jats:sup>) mice. In mice at 2 weeks of age there was a substantial reduction in myelin basic protein (MBP) mRNA and protein. This was confirmed by an immunohistochemical analysis. MBP mRNA and protein, however, reach normal levels at 3 weeks of age. Proteolipid protein (PLP) and MAL mRNA were also reduced in ASA<jats:sup>–/–</jats:sup> mice at 2 weeks of age; whereas the level of PLP mRNA was normal at 26 weeks of age, MAL mRNA expression remained reduced up to this age. <jats:italic>In situ</jats:italic> hybridization revealed no significant changes in the number of myelinating oligodendrocytes or oligodendrocyte precursor cells in ASA<jats:sup>–/–</jats:sup> mice. These results suggest that oligodendrocyte differentiation was normal in ASA<jats:sup>–/–</jats:sup> mice. No differences were found in the expression of the sulphatide synthesizing enzymes cerebroside sulphotransferase and UDP‐galactose : ceramide galactosyltransferase. Our data demonstrate a delay in myelin formation in ASA<jats:sup>–/–</jats:sup> mice. This raises the possibility that similar alterations in MLD patients may contribute to the pathology of the disease.</jats:p>