RGD Reference Report - A Critical Role for the Type I Interferon Receptor in Virus-Induced Autoimmune Diabetes in Rats. - Rat Genome Database

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A Critical Role for the Type I Interferon Receptor in Virus-Induced Autoimmune Diabetes in Rats.

Authors: Qaisar, Natasha  Lin, Suvana  Ryan, Glennice  Yang, Chaoxing  Oikemus, Sarah R  Brodsky, Michael H  Bortell, Rita  Mordes, John P  Wang, Jennifer P 
Citation: Qaisar N, etal., Diabetes. 2017 Jan;66(1):145-157. doi: 10.2337/db16-0462. Epub 2016 Oct 7.
RGD ID: 12910492
Pubmed: PMID:27999109   (View Abstract at PubMed)
PMCID: PMC5204313   (View Article at PubMed Central)
DOI: DOI:10.2337/db16-0462   (Journal Full-text)

The pathogenesis of human type 1 diabetes, characterized by immune-mediated damage of insulin-producing ß-cells of pancreatic islets, may involve viral infection. Essential components of the innate immune antiviral response, including type I interferon (IFN) and IFN receptor-mediated signaling pathways, are candidates for determining susceptibility to human type 1 diabetes. Numerous aspects of human type 1 diabetes pathogenesis are recapitulated in the LEW.1WR1 rat model. Diabetes can be induced in LEW.1WR1 weanling rats challenged with virus or with the viral mimetic polyinosinic:polycytidylic acid (poly I:C). We hypothesized that disrupting the cognate type I IFN receptor (type I IFN α/ß receptor [IFNAR]) to interrupt IFN signaling would prevent or delay the development of virus-induced diabetes. We generated IFNAR1 subunit-deficient LEW.1WR1 rats using CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) genome editing and confirmed functional disruption of the Ifnar1 gene. IFNAR1 deficiency significantly delayed the onset and frequency of diabetes and greatly reduced the intensity of insulitis after poly I:C treatment. The occurrence of Kilham rat virus-induced diabetes was also diminished in IFNAR1-deficient animals. These findings firmly establish that alterations in innate immunity influence the course of autoimmune diabetes and support the use of targeted strategies to limit or prevent the development of type 1 diabetes.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cytokine-mediated signaling pathway  IMP 12910492 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type I interferon signaling pathway  ISOIfnar1 (Rattus norvegicus)12910492; 12910492 RGD 
type I interferon signaling pathway  IMP 12910492 RGD 
Phenotype Annotations    Click to see Annotation Detail View
Objects Annotated

Genes (Rattus norvegicus)
Ifnar1  (interferon alpha and beta receptor subunit 1)
Ifnar1em1  (interferon alpha and beta receptor subunit 1; CRISPR/Cas9 induced mutant 1)
Ifnar1em2  (interferon alpha and beta receptor subunit 1; CRISPR/Cas9 induced mutant 2)

Genes (Mus musculus)
Ifnar1  (interferon (alpha and beta) receptor 1)

Genes (Homo sapiens)
IFNAR1  (interferon alpha and beta receptor subunit 1)

Objects referenced in this article
Gene IL15 interleukin 15 Homo sapiens
Gene Il15 interleukin 15 Mus musculus
Gene Il15 interleukin 15 Rattus norvegicus
Gene Il15em1Soar interleukin 15; ZFN induced mutant 1, Soar Rattus norvegicus
Strain SD-Il15em1Soar null Rattus norvegicus

Additional Information