Loss-of-function mutations in sodium channel Na(v)1.7 cause anosmia
- 13 April 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 472 (7342), 186-190
- https://doi.org/10.1038/nature09975
Abstract
Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Na(v)1.7, causes a congenital inability to experience pain in humans. Here we show that Na(v)1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Na(v)1.7 in odour perception, we generated conditional null mice in which Na(v)1.7 was removed from all olfactory sensory neurons. In the absence of Na(v)1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell.Keywords
This publication has 39 references indexed in Scilit:
- Age-induced disruption of selective olfactory bulb synaptic circuitsProceedings of the National Academy of Sciences of the United States of America, 2010
- The Vomeronasal Organ Mediates Interspecies Defensive Behaviors through Detection of Protein Pheromone HomologsCell, 2010
- Olfactory Dysfunction Correlates with Amyloid-β Burden in an Alzheimer's Disease Mouse ModelJournal of Neuroscience, 2010
- Better smelling through genetics: mammalian odor perceptionCurrent Opinion in Neurobiology, 2008
- Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epitheliumProceedings of the National Academy of Sciences of the United States of America, 2007
- Synapse‐specific localization of vesicular glutamate transporters in the rat olfactory bulbEuropean Journal of Neuroscience, 2007
- Coding and synaptic processing of sensory information in the glomerular layer of the olfactory bulbSeminars in Cell & Developmental Biology, 2006
- Central Role of the CNGA4 Channel Subunit in Ca 2+ -Calmodulin-Dependent Odor AdaptationScience, 2001
- X Inactivation of the OCNC1 Channel Gene Reveals a Role for Activity-Dependent Competition in the Olfactory SystemCell, 2001
- Rapid down-regulation of tyrosine hydroxylase expression in the olfactory bulb of naris-occluded adult ratsJournal of Comparative Neurology, 1996