Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases Journal Article
| Authors: | Phaneuf, D.; Wakamatsu, N.; Huang, J. Q.; Borowski, A.; Peterson, A. C.; Fortunato, S. R.; Ritter, G.; Igdoura, S. A.; Morales, C. R.; Benoit, G.; Akerman, B. R.; Leclerc, D.; Hanai, N.; Marth, J. D.; Trasler, J. M.; Gravel, R. A. |
| Article Title: | Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases |
| Abstract: | We have generated mouse models of human Tay-Sachs and Sandhoff diseases by targeted disruption of the Hexa (α subunit) or Hexb (β subunit) genes, respectively, encoding lysosomal β-hexosaminidase A (structure, α) and B (structure, ββ). Both mutant mice accumulate G(M2) ganglioside in brain, much more so in Hexb -/- mice, and the latter also accumulate glycolipid G(A2). Hexa -/- mice suffer no obvious behavioral or neurological deficit, while Hexb -/- mice develop a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor and ataxia. The Hexb -/- but not the Hexa -/- mice have massive depletion of spinal cord axons as an apparent consequence of neuronal storage of G(M2). We propose that Hexa -/- mice escape disease through partial catabolism of accumulated G(M2) via G(A2) (asialo-G(M2)) through the combined action of sialidase and β-hexosaminidase B. |
| Keywords: | controlled study; nonhuman; mouse; phenotype; animals; mice; mice, knockout; animal tissue; gene targeting; animal model; brain injuries; mice, inbred c57bl; animalia; liver; molecular sequence data; rna, messenger; gene disruption; spinal cord; sialidase; organ specificity; muscle weakness; base sequence; disease models, animal; tremor; ataxia; degenerative disease; ganglioside gm2; rigidity; catabolism; glycosphingolipids; brain chemistry; tay-sachs disease; beta-n-acetylhexosaminidase; tay sachs disease; g(m2) ganglioside; spasticity; humans; male; female; priority journal; article; sandhoff disease; beta n acetylhexosaminidase b |
| Journal Title: | Human Molecular Genetics |
| Volume: | 5 |
| Issue: | 1 |
| ISSN: | 0964-6906 |
| Publisher: | Oxford University Press |
| Date Published: | 1996-01-01 |
| Start Page: | 1 |
| End Page: | 14 |
| Language: | English |
| DOI: | 10.1093/hmg/5.1.1 |
| PUBMED: | 8789434 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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