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

Kazunori Sango, Shoji Yamanaka, Alexander Hoffmann, Yasuharu Okuda, Alexander Grinberg, Heiner Westphal, Michael Mcdonald, Jacqueline N. Crawley, Konrad Sandhoff, Kinuko Suzuki, Richard L. Proia

Research output: Contribution to journalArticle

324 Citations (Scopus)

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
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Sandhoff Disease
Gangliosides
Nervous System
Phenotype
Sphingolipidoses
G(M2) Ganglioside
Hexosaminidase A
Embryonic Stem Cells
Neurodegenerative Diseases
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Sango, K., Yamanaka, S., Hoffmann, A., Okuda, Y., Grinberg, A., Westphal, H., ... 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. https://doi.org/10.1038/ng1095-170

Mouse models of Tay–Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism. / Sango, Kazunori; Yamanaka, Shoji; Hoffmann, Alexander; Okuda, Yasuharu; Grinberg, Alexander; Westphal, Heiner; Mcdonald, Michael; Crawley, Jacqueline N.; Sandhoff, Konrad; Suzuki, Kinuko; Proia, Richard L.

In: Nature Genetics, Vol. 11, No. 2, 01.01.1995, p. 170-176.

Research output: Contribution to journalArticle

Sango, K, Yamanaka, S, Hoffmann, A, Okuda, Y, Grinberg, A, Westphal, H, Mcdonald, M, Crawley, JN, Sandhoff, K, Suzuki, K & Proia, RL 1995, 'Mouse models of Tay–Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism', Nature Genetics, vol. 11, no. 2, pp. 170-176. https://doi.org/10.1038/ng1095-170
Sango, Kazunori ; Yamanaka, Shoji ; Hoffmann, Alexander ; Okuda, Yasuharu ; Grinberg, Alexander ; Westphal, Heiner ; Mcdonald, Michael ; Crawley, Jacqueline N. ; Sandhoff, Konrad ; Suzuki, Kinuko ; Proia, Richard L. / Mouse models of Tay–Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism. In: Nature Genetics. 1995 ; Vol. 11, No. 2. pp. 170-176.
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