Adar1 deletion causes degeneration of the exocrine pancreas via Mavs-dependent interferon signaling.
Adar1
Interferon
Mavs
Mouse
Pancreatic development
Pancreatic homeostasis
Journal
Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744
Informations de publication
Date de publication:
15 01 2023
15 01 2023
Historique:
received:
15
07
2022
accepted:
21
11
2022
pmc-release:
16
01
2024
pubmed:
3
12
2022
medline:
18
1
2023
entrez:
2
12
2022
Statut:
ppublish
Résumé
Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-binding protein that deaminates adenosine (A) to inosine (I). A-to-I editing alters post-transcriptional RNA processing, making ADAR1 a crucial regulator of gene expression. Consequently, Adar1 has been implicated in organogenesis. To determine the role of Adar1 in pancreatic development and homeostasis, we conditionally deleted Adar1 from the murine pancreas (Ptf1aCre/+; Adar1Fl/Fl). The resulting mice had stunted growth, likely due to malabsorption associated with exocrine pancreatic insufficiency. Analyses of pancreata revealed ductal cell expansion, heightened interferon-stimulated gene expression and an increased influx of immune cells. Concurrent deletion of Adar1 and Mavs, a signaling protein implicated in the innate immune pathway, rescued the degenerative phenotype and resulted in normal pancreatic development. Taken together, our work suggests that the primary function of Adar1 in the pancreas is to prevent aberrant activation of the Mavs-mediated innate immune pathway, thereby maintaining pancreatic homeostasis.
Identifiants
pubmed: 36458554
pii: 286616
doi: 10.1242/dev.201097
pmc: PMC10110501
pii:
doi:
Substances chimiques
Interferons
9008-11-1
Adenosine Deaminase
EC 3.5.4.4
ADAR1 protein, mouse
EC 3.5.4.4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA237384
Pays : United States
Organisme : NCI NIH HHS
ID : NCI R37 (CA237384)
Pays : United States
Informations de copyright
© 2023. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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