title: Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism.
abstract: Tay-Sachs and Sandhoff diseases are clinically similar neurodegenerative disorders. These two sphingolipidoses are characterized by a heritable absence of beta-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.
authors.affiliation: Section on Biochemical Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: K
authors.initials: K
authors.lastname: Sango
authors.forename: S
authors.initials: S
authors.lastname: Yamanaka
authors.forename: A
authors.initials: A
authors.lastname: Hoffmann
authors.forename: Y
authors.initials: Y
authors.lastname: Okuda
authors.forename: A
authors.initials: A
authors.lastname: Grinberg
authors.forename: H
authors.initials: H
authors.lastname: Westphal
authors.forename: M P
authors.initials: MP
authors.lastname: McDonald
authors.forename: J N
authors.initials: JN
authors.lastname: Crawley
authors.forename: K
authors.initials: K
authors.lastname: Sandhoff
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: R L
authors.initials: RL
authors.lastname: Proia
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D002240:Carbohydrate Sequence; D004195:Disease Models, Animal; D005732:Gangliosides / Q000378:metabolism*; D054818:Hexosaminidase A; D054819:Hexosaminidase B; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D015183:Restriction Mapping; D012497:Sandhoff Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000502:physiology; D013661:Tay-Sachs Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001619:beta-N-Acetylhexosaminidases / Q000172:deficiency* / Q000235:genetics*
chemical_list: D005732:Gangliosides; D054818:Hexosaminidase A; D054819:Hexosaminidase B; D001619:beta-N-Acetylhexosaminidases