Behavioral characterization of a CRISPR-generated TRPA1 knockout rat in models of pain, itch, and asthma.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 01 2020
22 01 2020
Historique:
received:
25
09
2019
accepted:
03
01
2020
entrez:
24
1
2020
pubmed:
24
1
2020
medline:
20
11
2020
Statut:
epublish
Résumé
The transient receptor potential (TRP) superfamily of ion channels has garnered significant attention by the pharmaceutical industry. In particular, TRP channels showing high levels of expression in sensory neurons such as TRPV1, TRPA1, and TRPM8, have been considered as targets for indications where sensory neurons play a fundamental role, such as pain, itch, and asthma. Modeling these indications in rodents is challenging, especially in mice. The rat is the preferred species for pharmacological studies in pain, itch, and asthma, but until recently, genetic manipulation of the rat has been technically challenging. Here, using CRISPR technology, we have generated a TRPA1 KO rat to enable more sophisticated modeling of pain, itch, and asthma. We present a detailed phenotyping of the TRPA1 KO rat in models of pain, itch, and asthma that have previously only been investigated in the mouse. With the exception of nociception induced by direct TRPA1 activation, we have found that the TRPA1 KO rat shows apparently normal behavioral responses in multiple models of pain and itch. Immune cell infiltration into the lung in the rat OVA model of asthma, on the other hand, appears to be dependent on TRPA1, similar to was has been observed in TRPA1 KO mice. Our hope is that the TRPA1 KO rat will become a useful tool in further studies of TRPA1 as a drug target.
Identifiants
pubmed: 31969645
doi: 10.1038/s41598-020-57936-5
pii: 10.1038/s41598-020-57936-5
pmc: PMC6976688
doi:
Substances chimiques
TRPA1 Cation Channel
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
979Références
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