title: Loss-of-function mutations in sodium channel Nav1.7 cause anosmia.
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.
authors: Department of Physiology, University of Saarland School of Medicine, 66421 Homburg, Germany.
authors: Jan
authors: J
authors: Weiss
authors: Martina
authors: M
authors: Pyrski
authors: Eric
authors: E
authors: Jacobi
authors: Bernd
authors: B
authors: Bufe
authors: Vivienne
authors: V
authors: Willnecker
authors: Bernhard
authors: B
authors: Schick
authors: Philippe
authors: P
authors: Zizzari
authors: Samuel J
authors: SJ
authors: Gossage
authors: Charles A
authors: CA
authors: Greer
authors: Trese
authors: T
authors: Leinders-Zufall
authors: C Geoffrey
authors: CG
authors: Woods
authors: John N
authors: JN
authors: Wood
authors: Frank
authors: F
authors: Zufall
mesh_terms: D000200:Action Potentials; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009812:Odorants / Q000032:analysis; D000857:Olfaction Disorders / Q000151:congenital / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D009831:Olfactory Mucosa / Q000166:cytology / Q000473:pathology; D009833:Olfactory Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D055696:Olfactory Perception / Q000235:genetics / Q000502:physiology; D018034:Olfactory Receptor Neurons / Q000378:metabolism / Q000473:pathology; D010146:Pain / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D012903:Smell / Q000235:genetics / Q000502:physiology; D015222:Sodium Channels / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D014556:Urine / Q000737:chemistry
chemical_list: D050505:Mutant Proteins; D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; C503479:Scn9a protein, mouse; D015222:Sodium Channels