Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism

K. Sango, S. Yamanaka, A. Hoffmann, Y. Okuda, A. Grinberg, H. Westphal, M. P. McDonald, Jacqueline Crawley, K. Sandhoff, K. Suzuki, R. L. Proia

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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 G(M2) 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.

Original languageEnglish (US)
Pages (from-to)170-176
Number of pages7
JournalNature Genetics
Volume11
Issue number2
StatePublished - 1995
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Sango, K., Yamanaka, S., Hoffmann, A., Okuda, Y., Grinberg, A., Westphal, H., McDonald, M. P., Crawley, J., Sandhoff, K., Suzuki, K., & Proia, R. L. (1995). Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism. Nature Genetics, 11(2), 170-176.