Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases.


Journal Article

We have generated mouse models of human Tay-Sachs and Sandhoff diseases by targeted disruption of the Hexa (alpha subunit) or Hexb (beta subunit) genes, respectively, encoding lysosomal beta-hexosaminidase A (structure, alpha) and B (structure, beta beta). Both mutant mice accumulate GM2 ganglioside in brain, much more so in Hexb -/- mice, and the latter also accumulate glycolipid GA2. 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 GM2. We propose that Hexa -/- mice escape disease through partial catabolism of accumulated GM2 via GA2 (asialo-GM2) through the combined action of sialidase and beta-hexosaminidase B.

Full Text

Cited Authors

  • Phaneuf, D; Wakamatsu, N; Huang, JQ; Borowski, A; Peterson, AC; Fortunato, SR; Ritter, G; Igdoura, SA; Morales, CR; Benoit, G; Akerman, BR; Leclerc, D; Hanai, N; Marth, JD; Trasler, JM; Gravel, RA

Published Date

  • January 1, 1996

Published In

Volume / Issue

  • 5 / 1

Start / End Page

  • 1 - 14

PubMed ID

  • 8789434

Pubmed Central ID

  • 8789434

Electronic International Standard Serial Number (EISSN)

  • 1460-2083

International Standard Serial Number (ISSN)

  • 0964-6906

Digital Object Identifier (DOI)

  • 10.1093/hmg/5.1.1


  • eng