Mouse models of Tay–Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism
- 1 October 1995
- journal article
- research article
- Published by Springer Nature in Nature Genetics
- Vol. 11 (2), 170-176
- https://doi.org/10.1038/ng1095-170
Abstract
Tay–Sachs and Sandhoff diseases are clinically similar neurodegenerative disorders. These two sphingolipidoses are characterized by a heritable absence of β–hexosaminidase A resulting in defective GM2 ganglioside degradation. Through disruption of the Hexa and Hexb genes in embryonic stem cells, we have established mouse models corresponding to each disease. Unlike the two human disorders, the two mouse models show very different neurologic phenotypes. Although exhibiting biochemical and pathologic features of the disease, the Tay–Sachs model showed no neurological abnormalities. In contrast, the Sandhoff model was severely affected. The phenotypic difference between the two mouse models is the result of differences in the ganglioside degradation pathway between mice and humans.Keywords
This publication has 19 references indexed in Scilit:
- The Degradative Pathway of Gangliosides GM1 and GM2 in Neuro2a Cells by SialidaseJournal of Neurochemistry, 2002
- Biochemical Basis of Late-Onset NeurolipidosesDevelopmental Neuroscience, 1991
- Neuropathology of Late Onset GangliosidosesDevelopmental Neuroscience, 1991
- Altering the Genome by Homologous RecombinationScience, 1989
- Incorporation and metabolism of ganglioside GM2 in skin fibroblasts from normal and GM2 gangliosidosis subjectsEuropean Journal of Biochemistry, 1985
- Activating Proteins for Ganglioside GM2Degradation by β-Hexosaminidase Isoenzymes in Tissue Extracts from Different SpeciesHoppe-Seyler´s Zeitschrift Für Physiologische Chemie, 1983
- Purification and Characterization of an Activator Protein for the Degradation of Glycolipids GM2and GA2by Hexosaminidase AHoppe-Seyler´s Zeitschrift Für Physiologische Chemie, 1979
- A simple and novel method for tritium labeling of gangliosides and other sphingolipidsBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1978
- The Biochemistry of Sphingolipid Storage DiseasesAngewandte Chemie International Edition in English, 1977
- ENZYME ALTERATIONS AND LIPID STORAGE IN THREE VARIANTS OF TAY‐SACHS DISEASEJournal of Neurochemistry, 1971