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Sustained in vivo inhibition of protein domains using single-chain Fv recombinant antibodies and its application to dissect RGMa activity on axonal outgrowth.

Authors
  • Tassew, Nardos G
  • Charish, Jason
  • Chestopalova, Larisa
  • Monnier, Philippe P
Type
Published Article
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Publication Date
Jan 28, 2009
Volume
29
Issue
4
Pages
1126–1131
Identifiers
DOI: 10.1523/JNEUROSCI.5385-08.2009
PMID: 19176821
Source
Medline
License
Unknown

Abstract

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.

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