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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cruz-aguado, R. Lam, C. K. Barbieri, M. A. Helm, J. R. Gerrow, K. Hayden, M. R. El-husseini, A. E. Orban, P. C. Cao, L. P. Bissada, N. Devon, R. S. Davidson, T-l Tetzlaff, W. Mccaffery, J. M. Leavitt, B. R. Schwab, C. Witmer, J. Metzler, M. Simpson, E. M. |
| Description | Author Affiliation: Devon RS ( Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4.); |
| Abstract | ALS2 is an autosomal recessive form of spastic paraparesis (motor neuron disease) with juvenile onset and slow progression caused by loss of function of alsin, an activator of Rac1 and Rab5 small GTPases. To establish an animal model of ALS2 and derive insights into the pathogenesis of this illness, we have generated alsin-null mice. Cytosol from brains of Als2(-/-) mice shows marked diminution of Rab5-dependent endosome fusion activity. Furthermore, primary neurons from Als2(-/-) mice show a disturbance in endosomal transport of insulin-like growth factor 1 (IGF1) and BDNF receptors, whereas neuronal viability and endocytosis of transferrin and dextran seem unaltered. There is a significant decrease in the size of cortical motor neurons, and Als2(-/-) mice are mildly hypoactive. Altered trophic receptor trafficking in neurons of Als2(-/-) mice may underlie the histopathological and behavioral changes observed and the pathogenesis of ALS2. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 25 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Endosomes Metabolism Guanine Nucleotide Exchange Factors Deficiency Motor Neurons Pathology Motor Skills Disorders Physiopathology Animals Behavior, Animal Body Weight Cytosol Endocytosis Genetics Mice Mice, Inbred C57BL Mice, Knockout Motor Activity Physical Conditioning, Animal Protein Transport Receptor, TrkB Time Factors Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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