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The Journal of Neuroscience, January 28, 2009, 29(4):1126-1131; doi:10.1523/JNEUROSCI.5385-08.2009

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Brief Communications
Sustained In Vivo Inhibition of Protein Domains Using Single-Chain Fv Recombinant Antibodies and Its Application to Dissect RGMa Activity on Axonal Outgrowth

Nardos G. Tassew,^1,2 Jason Charish,^1,2 Larisa Chestopalova,¹ and Philippe P. Monnier^1,2,3

¹Genetics and Development Division, Toronto Western Research Institute, Toronto, Ontario, Canada M5T 2S8, ²Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8, and ³Department of Ophthalmology and Vision Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5T 1R4

Correspondence should be addressed to Philippe P. Monnier, Toronto Western Research Institute, 399 Bathurst Street, MCL 6-412, Toronto, Ontario, Canada M5T 2S8. Email: pmonnier{at}uhnres.utoronto.ca

Antibodies are powerful tools for delineating the specific function of protein domains, yet several limitations restrict their in vivo applicability. Here we present a new method to obtain sustained in vivo inhibition of specific protein domains using recombinant antibodies. We show that long term in vivo expression of single-chain Fv (scFv) fragments in the developing CNS can be achieved through retroviral transduction. Moreover, specific scFvs generated against the N- and C-terminal domains of the repulsive guidance molecule, RGMa, prevent proper axon targeting in the visual system. This work reveals a previously unappreciated role for the RGMa N-terminal domain in axon guidance, and provides a novel, broadly applicable and rapid procedure to functionally antagonize any protein domain in vivo.

Key words: repulsive guidance molecule; developing visual pathway; recombinant antibodies; scFvs; protein domains; axon guidance

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Received Nov. 7, 2008; revised Dec. 8, 2008; accepted Dec. 11, 2008.

Correspondence should be addressed to Philippe P. Monnier, Toronto Western Research Institute, 399 Bathurst Street, MCL 6-412, Toronto, Ontario, Canada M5T 2S8. Email: pmonnier{at}uhnres.utoronto.ca

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