The Human SCN10AG1662S Point Mutation Established in Mice Impacts on Mechanical, Heat, and Cool Sensitivity
The voltage-gated sodium channel NAV1.8 is expressed in primary nociceptive neurons and is involved in pain transmission. Mutations in the SCN10A gene (encoding NAV1.8 channel) have been identified in patients with idiopathic painful small fiber neuropathy (SFN) including the SCN10AG1662S gain-of-fu...
Guardado en:
| Autores principales: | , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/a4ec1bec8bdc4df38529cb787b6a3428 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:a4ec1bec8bdc4df38529cb787b6a3428 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:a4ec1bec8bdc4df38529cb787b6a34282021-12-01T23:50:51ZThe Human SCN10AG1662S Point Mutation Established in Mice Impacts on Mechanical, Heat, and Cool Sensitivity1663-981210.3389/fphar.2021.780132https://doaj.org/article/a4ec1bec8bdc4df38529cb787b6a34282021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.780132/fullhttps://doaj.org/toc/1663-9812The voltage-gated sodium channel NAV1.8 is expressed in primary nociceptive neurons and is involved in pain transmission. Mutations in the SCN10A gene (encoding NAV1.8 channel) have been identified in patients with idiopathic painful small fiber neuropathy (SFN) including the SCN10AG1662S gain-of-function mutation. However, the role of this mutation in pain sensation remains unknown. We have generated the first mouse model for the G1662S mutation by using homologous recombination in embryonic stem cells. The corresponding Scn10aG1663S mouse line has been analyzed for Scn10a expression, intraepidermal nerve fiber density (IENFD), and nociception using behavioral tests for thermal and mechanical sensitivity. The Scn10aG1663S mutants had a similar Scn10a expression level in dorsal root ganglia (DRG) to their wild-type littermates and showed normal IENFD in hindpaw skin. Mutant mice were more sensitive to touch than wild types in the von Frey test. In addition, sexual dimorphism was observed for several pain tests, pointing to the relevance of performing the phenotypical assessment in both sexes. Female homozygous mutants tended to be more sensitive to cooling stimuli in the acetone test. For heat sensitivity, male homozygous mutants showed shorter latencies to radiant heat in the Hargreaves test while homozygous females had longer latencies in the tail flick test. In addition, mutant males displayed a shorter reaction latency on the 54°C hot plate. Collectively, Scn10aG1663S mutant mice show a moderate but consistent increased sensitivity in behavioral tests of nociception. This altered nociception found in Scn10aG1663S mice demonstrates that the corresponding G1662 mutation of SCN10A found in SFN patients with pain contributes to their pain symptoms.Celeste ChidiacYaping XueMaria del Mar Muniz MorenoAmeer Abu Bakr RasheedRomain LorentzMarie-Christine BirlingClaire Gaveriaux-RuffYann HeraultYann HeraultFrontiers Media S.A.articleSCN10Asodium channelsmall fiber neuropathynociceptionneuropathic painstatistical modellingTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
SCN10A sodium channel small fiber neuropathy nociception neuropathic pain statistical modelling Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
SCN10A sodium channel small fiber neuropathy nociception neuropathic pain statistical modelling Therapeutics. Pharmacology RM1-950 Celeste Chidiac Yaping Xue Maria del Mar Muniz Moreno Ameer Abu Bakr Rasheed Romain Lorentz Marie-Christine Birling Claire Gaveriaux-Ruff Yann Herault Yann Herault The Human SCN10AG1662S Point Mutation Established in Mice Impacts on Mechanical, Heat, and Cool Sensitivity |
| description |
The voltage-gated sodium channel NAV1.8 is expressed in primary nociceptive neurons and is involved in pain transmission. Mutations in the SCN10A gene (encoding NAV1.8 channel) have been identified in patients with idiopathic painful small fiber neuropathy (SFN) including the SCN10AG1662S gain-of-function mutation. However, the role of this mutation in pain sensation remains unknown. We have generated the first mouse model for the G1662S mutation by using homologous recombination in embryonic stem cells. The corresponding Scn10aG1663S mouse line has been analyzed for Scn10a expression, intraepidermal nerve fiber density (IENFD), and nociception using behavioral tests for thermal and mechanical sensitivity. The Scn10aG1663S mutants had a similar Scn10a expression level in dorsal root ganglia (DRG) to their wild-type littermates and showed normal IENFD in hindpaw skin. Mutant mice were more sensitive to touch than wild types in the von Frey test. In addition, sexual dimorphism was observed for several pain tests, pointing to the relevance of performing the phenotypical assessment in both sexes. Female homozygous mutants tended to be more sensitive to cooling stimuli in the acetone test. For heat sensitivity, male homozygous mutants showed shorter latencies to radiant heat in the Hargreaves test while homozygous females had longer latencies in the tail flick test. In addition, mutant males displayed a shorter reaction latency on the 54°C hot plate. Collectively, Scn10aG1663S mutant mice show a moderate but consistent increased sensitivity in behavioral tests of nociception. This altered nociception found in Scn10aG1663S mice demonstrates that the corresponding G1662 mutation of SCN10A found in SFN patients with pain contributes to their pain symptoms. |
| format |
article |
| author |
Celeste Chidiac Yaping Xue Maria del Mar Muniz Moreno Ameer Abu Bakr Rasheed Romain Lorentz Marie-Christine Birling Claire Gaveriaux-Ruff Yann Herault Yann Herault |
| author_facet |
Celeste Chidiac Yaping Xue Maria del Mar Muniz Moreno Ameer Abu Bakr Rasheed Romain Lorentz Marie-Christine Birling Claire Gaveriaux-Ruff Yann Herault Yann Herault |
| author_sort |
Celeste Chidiac |
| title |
The Human SCN10AG1662S Point Mutation Established in Mice Impacts on Mechanical, Heat, and Cool Sensitivity |
| title_short |
The Human SCN10AG1662S Point Mutation Established in Mice Impacts on Mechanical, Heat, and Cool Sensitivity |
| title_full |
The Human SCN10AG1662S Point Mutation Established in Mice Impacts on Mechanical, Heat, and Cool Sensitivity |
| title_fullStr |
The Human SCN10AG1662S Point Mutation Established in Mice Impacts on Mechanical, Heat, and Cool Sensitivity |
| title_full_unstemmed |
The Human SCN10AG1662S Point Mutation Established in Mice Impacts on Mechanical, Heat, and Cool Sensitivity |
| title_sort |
human scn10ag1662s point mutation established in mice impacts on mechanical, heat, and cool sensitivity |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/a4ec1bec8bdc4df38529cb787b6a3428 |
| work_keys_str_mv |
AT celestechidiac thehumanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT yapingxue thehumanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT mariadelmarmunizmoreno thehumanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT ameerabubakrrasheed thehumanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT romainlorentz thehumanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT mariechristinebirling thehumanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT clairegaveriauxruff thehumanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT yannherault thehumanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT yannherault thehumanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT celestechidiac humanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT yapingxue humanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT mariadelmarmunizmoreno humanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT ameerabubakrrasheed humanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT romainlorentz humanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT mariechristinebirling humanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT clairegaveriauxruff humanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT yannherault humanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity AT yannherault humanscn10ag1662spointmutationestablishedinmiceimpactsonmechanicalheatandcoolsensitivity |
| _version_ |
1718404004868784128 |