Journal Article

Dramatically Different Phenotypes in Mouse Models of Human Tay-Sachs and Sandhoff Diseases

Daniel Phaneuf, Nobuaki Wakamatsu, Jing-Qi Huang, Anita Borowski, Alan C. Peterson, Sheila R. Fortunato, Gerd Ritter, Suleiman A. Igdoura, Carlos R. Morales, Guylaine Benoit, Beverly R. Akerman, Daniel Leclerc, Nobuo Hanai, Jamey D. Marth, Jacquetta M. Trasler and Roy A. Gravel

in Human Molecular Genetics

Volume 5, issue 1, pages 1-14
Published in print January 1996 | ISSN: 0964-6906
e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/5.1.1
Dramatically Different Phenotypes in Mouse Models of Human Tay-Sachs and Sandhoff Diseases

Show Summary Details

Preview

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 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 β-hexosaminidase B.

Journal Article.  8521 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.