Human Molecular Genetics, Vol 6, 205-211, Copyright © 1997 by Oxford University Press
CN Hahn, M del Pilar Martin, M Schroder, MT Vanier, Y Hara, K Suzuki, K Suzuki and A d'Azzo
Human GM1-gangliosidosis is caused by a genetic deficiency of lysosomal
acid beta-galactosidase (beta-gal). The disease manifests itself either as
an infantile, juvenile or adult form and is primarily a neurological
disorder with progressive brain dysfunction. A mouse model lacking a
functional beta-gal gene has been generated by homologous recombination and
embryonic stem cell technology. Tissues from affected mice are devoid of
beta-gal mRNA and totally deficient in GM1-ganglioside- hydrolyzing
capacity. Storage material was already conspicuous in the brain at 3 weeks.
By 5 weeks, extensive storage of periodic acid Schiff- positive material
was observed in neurons throughout the brain and spinal cord. Consistent
with the neuropathology, abnormal accumulation of GM1-ganglioside in the
brain progressed from twice to almost five times the normal amount during
the period from 3 weeks to 3.5 months. Despite the accumulation of brain
GM1-ganglioside at the level equal to or exceeding that seen in gravely ill
human patients, these mice show no overt clinical phenotype up to 4-5
months. However, tremor, ataxia and abnormal gait become apparent in older
mice. Thus, the beta-gal- deficient mice appear to mimic closely the
pathological, biochemical and clinical abnormalities of the human disease.
ARTICLES
Generalized CNS disease and massive GM1-ganglioside accumulation in mice defective in lysosomal acid beta-galactosidase
Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. V. Bax, U. R. Rodgers, M. M. M. Bilek, and A. S. Weiss Cell Adhesion to Tropoelastin Is Mediated via the C-terminal GRKRK Motif and Integrin {alpha}V{beta}3 J. Biol. Chem., October 16, 2009; 284(42): 28616 - 28623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sakai, Y. Tanaka, M. Tanaka, N. Ban, K. Yamada, Y. Matsumura, D. Watanabe, M. Sasaki, T. Kita, and N. Inagaki ABCA2 Deficiency Results in Abnormal Sphingolipid Metabolism in Mouse Brain J. Biol. Chem., July 6, 2007; 282(27): 19692 - 19699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Gadola, J. D. Silk, A. Jeans, P. A. Illarionov, M. Salio, G. S. Besra, R. Dwek, T. D. Butters, F. M. Platt, and V. Cerundolo Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases J. Exp. Med., October 2, 2006; 203(10): 2293 - 2303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Sano, A. Tessitore, A. Ingrassia, and A. d'Azzo Chemokine-induced recruitment of genetically modified bone marrow cells into the CNS of GM1-gangliosidosis mice corrects neuronal pathology Blood, October 1, 2005; 106(7): 2259 - 2268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Kasperzyk, A. d'Azzo, F. M. Platt, J. Alroy, and T. N. Seyfried Substrate reduction reduces gangliosides in postnatal cerebrum-brainstem and cerebellum in GM1 gangliosidosis mice J. Lipid Res., April 1, 2005; 46(4): 744 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tomatsu, K. O. Orii, C. Vogler, J. Nakayama, B. Levy, J. H. Grubb, M. A. Gutierrez, S. Shim, S. Yamaguchi, T. Nishioka, et al. Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-) produced by targeted disruption of the gene defective in Morquio A disease Hum. Mol. Genet., December 15, 2003; 12(24): 3349 - 3358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Jeyakumar, R. Thomas, E. Elliot-Smith, D. A. Smith, A. C. van der Spoel, A. d'Azzo, V. Hugh Perry, T. D. Butters, R. A. Dwek, and F. M. Platt Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis Brain, April 1, 2003; 126(4): 974 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Nowroozi, T. Kawata, P. Liu, D. Rice, and J. H. Zernik High {beta}-Galactosidase and Ganglioside GM1 Levels in the Human Parotid Gland Arch Otolaryngol Head Neck Surg, November 1, 2001; 127(11): 1381 - 1384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tohyama, M. T. Vanier, K. Suzuki, T. Ezoe, J. Matsuda, and K. Suzuki Paradoxical influence of acid {beta}-galactosidase gene dosage on phenotype of the twitcher mouse (genetic galactosylceramidase deficiency) Hum. Mol. Genet., July 1, 2000; 9(11): 1699 - 1707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. van der Spoel, E. Bonten, and A. d'Azzo Processing of Lysosomal beta -Galactosidase. THE C-TERMINAL PRECURSOR FRAGMENT IS AN ESSENTIAL DOMAIN OF THE MATURE ENZYME J. Biol. Chem., March 31, 2000; 275(14): 10035 - 10040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Li, W.-H. Yu, N. Rozengurt, H.-Z. Zhao, K. M. Lyons, S. Anagnostaras, M. S. Fanselow, K. Suzuki, M. T. Vanier, and E. F. Neufeld Mouse model of Sanfilippo syndrome type B produced by targeted disruption of the gene encoding alpha -N-acetylglucosaminidase PNAS, December 7, 1999; 96(25): 14505 - 14510. [Abstract] [Full Text] [PDF]
|
|