Conditional, genetic disruption of ciliary neurotrophic factor receptors reveals a role in adult motor neuron survival.

Abstract

Indirect evidence suggests that endogenous ciliary neurotrophic factor (CNTF) receptor signaling can promote motor neuron (MN) survival in the adult. If so, proper targeting of this signaling may selectively counteract the effects of adult MN diseases. However, direct evidence for CNTF receptor involvement in adult MN survival is lacking, presumably because the unconditional blockade of the mouse CNTF receptor in vivo [through genetic disruption of the essential CNTF receptor alpha (CNTFRalpha) gene] leads to uniform perinatal death of the mice. To overcome this limitation, we have developed a method to selectively disrupt CNTF receptor function in a targeted subset of adult MNs that are not required for survival. A 'floxed CNTFRalpha' mouse line was generated and characterized. In addition, an adeno-associated virus (AAV) vector that drives Cre recombinase (Cre) expression was constructed and shown, with reporter mouse lines, to selectively excise floxed genes in facial MNs following its stereotaxic injection into the facial motor nucleus. Adult floxed CNTFRalpha mice were then injected with the AAV-Cre vector to excise the CNTFRalpha gene in the targeted MNs. The resulting data indicate that adult CNTF receptor signaling, likely by the MNs themselves, can play an essential role in MN survival. The data further indicate that this role is independent of any developmental contributions CNTF receptor signaling makes to MN survival or function.

• Authors: Nancy Lee, Rachel Robitz, Rebekah J Zurbrugg, Adam M Karpman, Ashley M Mahler, Samantha A Cronier, Rachel Vesey, Rachel P Spearry, Sergei Zolotukhin, A John Maclennan
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 27 Issue 11 Pg. 2830-7 (Jun 2008) ISSN: 1460-9568 [Electronic] France
• PMID: 18588528 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Ciliary Neurotrophic Factor
• Receptor, Ciliary Neurotrophic Factor
• Cre recombinase
• Integrases

Topics

• Age Factors
• Animals
• Cell Survival (genetics)
• Central Nervous System (metabolism)
• Ciliary Neurotrophic Factor (metabolism)
• Dependovirus (genetics)
• Down-Regulation (genetics)
• Facial Nerve (cytology, metabolism)
• Gene Targeting (methods)
• Genetic Vectors (genetics)
• Integrases (genetics)
• Mice
• Mice, Knockout
• Motor Neurons (metabolism)
• Receptor, Ciliary Neurotrophic Factor (genetics)
• Signal Transduction (genetics)
• Transfection