Development and characterization of type I interferon receptor knockout sheep: A model for viral immunology and reproductive signaling.

Autor:	Davies CJ; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States.; Center for Integrated BioSystems, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Fan Z; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Morgado KP; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States.; Center for Integrated BioSystems, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Liu Y; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Regouski M; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Meng Q; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Thomas AJ; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States.; Center for Integrated BioSystems, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Yun SI; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Song BH; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Frank JC; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Perisse IV; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Van Wettere A; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Lee YM; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States., Polejaeva IA; Department of Animal, Dairy and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2022 Sep 14; Vol. 13, pp. 986316. Date of Electronic Publication: 2022 Sep 14 (Print Publication: 2022).
DOI:	10.3389/fgene.2022.986316
Abstrakt:	Type I interferons (IFNs) initiate immune responses to viral infections. Their effects are mediated by the type I IFN receptor, IFNAR, comprised of two subunits: IFNAR1 and IFNAR2. One or both chains of the sheep IFNAR were disrupted in fetal fibroblast lines using CRISPR/Cas9 and 12 lambs were produced by somatic cell nuclear transfer (SCNT). Quantitative reverse transcription-polymerase chain reaction for IFN-stimulated gene expression showed that IFNAR deficient sheep fail to respond to IFN-alpha. Furthermore, fibroblast cells from an IFNAR2 -/- fetus supported significantly higher levels of Zika virus (ZIKV) replication than wild-type fetal fibroblast cells. Although many lambs have died from SCNT related problems or infections, one fertile IFNAR2 -/- ram lived to over 4 years of age, remained healthy, and produced more than 80 offspring. Interestingly, ZIKV infection studies failed to demonstrate a high level of susceptibility. Presumably, these sheep compensated for a lack of type I IFN signaling using the type II, IFN-gamma and type III, IFN-lambda pathways. These sheep constitute a unique model for studying the pathogenesis of viral infection. Historical data supports the concept that ruminants utilize a novel type I IFN, IFN-tau, for pregnancy recognition. Consequently, IFNAR deficient ewes are likely to be infertile, making IFNAR knockout sheep a valuable model for studying pregnancy recognition. A breeding herd of 32 IFNAR2 +/- ewes, which are fertile, has been developed for production of IFNAR2 -/- sheep for both infection and reproduction studies. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Davies, Fan, Morgado, Liu, Regouski, Meng, Thomas, Yun, Song, Frank, Perisse, Van Wettere, Lee and Polejaeva.)
Databáze:	MEDLINE
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