Human Molecular Genetics, Vol 5, 1-14, Copyright © 1996 by Oxford University Press
D Phaneuf, N Wakamatsu, JQ Huang, A Borowski, AC Peterson, SR Fortunato, G Ritter, SA Igdoura, CR Morales, G Benoit, BR Akerman, D Leclerc, N Hanai, JD Marth, JM Trasler and RA Gravel
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.
ARTICLES
Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases
Department of Pediatrics, McGill University, Montreal, Canada.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Sun, D. P. Witte, H. Ran, M. Zamzow, S. Barnes, H. Cheng, X. Han, M. T. Williams, M. R. Skelton, C. V. Vorhees, et al. Neurological deficits and glycosphingolipid accumulation in saposin B deficient mice Hum. Mol. Genet., August 1, 2008; 17(15): 2345 - 2356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Martin, V. Atmuri, R. J. Hemming, J. Farley, J. S. Mort, S. Byers, S. Hombach-Klonisch, R. Stern, and B. L. Triggs-Raine A mouse model of human mucopolysaccharidosis IX exhibits osteoarthritis Hum. Mol. Genet., July 1, 2008; 17(13): 1904 - 1915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Seyrantepe, M. Canuel, S. Carpentier, K. Landry, S. Durand, F. Liang, J. Zeng, A. Caqueret, R. A. Gravel, S. Marchesini, et al. Mice deficient in Neu4 sialidase exhibit abnormal ganglioside catabolism and lysosomal storage Hum. Mol. Genet., June 1, 2008; 17(11): 1556 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ramakrishnan, K. K. Hedayati, R. Lullmann-Rauch, C. Wessig, S. N. Fewou, H. Maier, H.-H. Goebel, V. Gieselmann, and M. Eckhardt Increasing Sulfatide Synthesis in Myelin-Forming Cells of Arylsulfatase A-Deficient Mice Causes Demyelination and Neurological Symptoms Reminiscent of Human Metachromatic Leukodystrophy J. Neurosci., August 29, 2007; 27(35): 9482 - 9490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sango, M. Takano, K. Ajiki, A. Tokashiki, N. Arai, H. Kawano, H. Horie, and S. Yamanaka Impaired Neurite Outgrowth in the Retina of a Murine Model of Sandhoff Disease Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3420 - 3425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hermo, H. I. Adamali, and J. M. Trasler Postnatal Development and Regulation of {beta}-Hexosaminidase in Epithelial Cells of the Rat Epididymis J Androl, January 1, 2004; 25(1): 69 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Luedtke, S. Andonian, S. Igdoura, and L. Hermo Cathepsin A Is Expressed in a Cell- and Region-specific Manner in the Testis and Epididymis and Is Not Regulated by Testicular or Pituitary Factors J. Histochem. Cytochem., August 1, 2000; 48(8): 1131 - 1146. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. Bertoni, Y.-T. Li, and S.-C. Li Catabolism of Asialo-GM2 in Man and Mouse. SPECIFICITY OF HUMAN/MOUSE CHIMERIC GM2 ACTIVATOR PROTEINS J. Biol. Chem., October 1, 1999; 274(40): 28612 - 28618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mathur, H. F. Sims, D. Gopalakrishnan, B. Gibson, P. Rinaldo, J. Vockley, G. Hug, and A. W. Strauss Molecular Heterogeneity in Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency Causing Pediatric Cardiomyopathy and Sudden Death Circulation, March 16, 1999; 99(10): 1337 - 1343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Trasler, F. Saberi, I. H. Somani, H. I. Adamali, J.-Q. Huang, S. R. Fortunato, G. Ritter, M. Gu, R. Aebersold, R. A. Gravel, et al. Characterization of the Testis and Epididymis in Mouse Models of Human Tay Sachs and Sandhoff Diseases and Partial Determination of Accumulated Gangliosides Endocrinology, July 1, 1998; 139(7): 3280 - 3288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Yuziuk, C. Bertoni, T. Beccari, A. Orlacchio, Y.-Y. Wu, S.-C. Li, and Y.-T. Li Specificity of Mouse GM2 Activator Protein and beta -N-Acetylhexosaminidases A and B. SIMILARITIES AND DIFFERENCES WITH THEIR HUMAN COUNTERPARTS IN THE CATABOLISM OF GM2 J. Biol. Chem., January 2, 1998; 273(1): 66 - 72. [Abstract] [Full Text] [PDF]
|
|