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Als2-deficient mice exhibit disturbances in endosome trafficking associated with motor behavioral abnormalities

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Devon, R. S., Orban, P. C., Gerrow, K., Barbieri, M. A., Schwab, C., Cao, L. P., Helm, J. R., Bissada, N., Cruz-Aguado, R., Davidson, T.-L., Witmer, J., Metzler, M., Lam, C. K., Tetzlaff, W., Simpson, E. M., McCaffery, J. M., El-Husseini, A. E., Leavitt, B. R., Hayden, M. R., & Zoghbi, H. Y. (2006). Als2-deficient mice exhibit disturbances in endosome trafficking associated with motor behavioral abnormalities. Proceedings of the National Academy of Sciences of the United States of America, 103(25), 9595-9600. https://doi.org/10.1073/pnas.0510197103

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Details
Author(s)

Devon, R. S.
Orban, P. C.
Gerrow, K.
Barbieri, M. A.
Schwab, C.
Cao, L. P.
Helm, J. R.
Bissada, N.
Cruz-Aguado, Reyniel
Davidson, T.-L.
Witmer, J.
Metzler, M.
Lam, C. K.􏰀
Tetzlaff, W.􏰀
Simpson, E. M.
McCaffery, J. M.
El-Husseini, A. E.
Leavitt, B. R.
Hayden, M. R.

Editor(s)

Zoghbi, Huda Y.

Title

Als2-deficient mice exhibit disturbances in endosome trafficking associated with motor behavioral abnormalities

Publication Type

article

Date issued

2006

Journal/Book/Host Title

Proceedings of the National Academy of Sciences of the United States of America

Volume

103

Issue

25

Start Page

9595

End Page

9600

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 diminu- tion of Rab5-dependent endosome fusion activity. Furthermore, primary neurons from Als2 mice show a disturbance in endo- somal transport of insulin-like growth factor 1 (IGF1) and BDNF receptors, whereas neuronal viability and endocytosis of trans- ferrin 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.

Full Text / URL

https://www.jstor.org/stable/30050954

URI

https://www.pnas.org/content/pnas/103/25/9595.full.pdf

DOI

10.1073/pnas.0510197103

ISSN

00278424

Publication note

final article published

Author Keywords

motor neuron
Rab5
ALS
alsin
knockout mouse

Publisher

National Academy of Sciences

Peer reviewed?

Peer reviewed

Use rights

http://rightsstatements.org/vocab/InC-EDU/1.0/
©2006. National Academy of Sciences.