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 language | English (US) |
|---|---|
| Pages (from-to) | 170-176 |
| Number of pages | 7 |
| Journal | Nature Genetics |
| Volume | 11 |
| Issue number | 2 |
| State | Published - 1995 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism. / Sango, K.; Yamanaka, S.; Hoffmann, A.; Okuda, Y.; Grinberg, A.; Westphal, H.; McDonald, M. P.; Crawley, Jacqueline; Sandhoff, K.; Suzuki, K.; Proia, R. L.
In: Nature Genetics, Vol. 11, No. 2, 1995, p. 170-176.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism
AU - Sango, K.
AU - Yamanaka, S.
AU - Hoffmann, A.
AU - Okuda, Y.
AU - Grinberg, A.
AU - Westphal, H.
AU - McDonald, M. P.
AU - Crawley, Jacqueline
AU - Sandhoff, K.
AU - Suzuki, K.
AU - Proia, R. L.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0029113867&partnerID=8YFLogxK
M3 - Article
C2 - 7550345
AN - SCOPUS:0029113867
VL - 11
SP - 170
EP - 176
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 2
ER -