Franken S, Wittke D, Mansson J E, D'Hooge R, De Deyn P P, Lüllmann-Rauch R, Matzner U, Gieselmann V
Department of Physiological Chemistry, University of Bonn, Germany.
Lipids Health Dis. 2006 Aug 7;5:21. 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.
芳基硫酸酯酶A（ASA）缺陷型小鼠是溶酶体贮积病异染性脑白质营养不良的模型。这种脂质沉积病的特征是鞘脂硫苷在溶酶体中蓄积。这种脂质的蓄积与进行性脱髓鞘有关。我们已将ASA缺陷型小鼠与UDP-半乳糖：神经酰胺-半乳糖基转移酶（CGT）无功能等位基因的杂合小鼠进行交配。已知这种缺陷会导致半乳糖基神经酰胺和硫苷的合成减少，这应会减少硫苷的蓄积并改善ASA缺陷型小鼠的病理状况。
然而，ASA-/- CGT+/-小鼠的硫苷蓄积未见明显减少。然而，内耳螺旋神经节细胞的神经元变性有所减轻。行为测试显示ASA-/- CGT+/-小鼠的表型有微小但明显的改善。
因此，通过基因手段减少半乳糖基神经酰胺和硫苷的生物合成总体上会使病理状况有适度改善。
