Evidence map›Paper›PMID 42261664›Full record

ArticleBiology of reproduction2026

Pregnancy in type I interferon receptor (IFNAR2) knockout sheep challenges the accepted paradigm for pregnancy recognition in ruminants†.

Christopher J Davies, Evan K Peterson, Aaron J Thomas, Andrea L Giles, Young-Min Lee, Irina A Polejaeva, Heloisa M Rutigliano

Abstract read
In one paragraph

Article in Biology of reproduction, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Christopher J DaviesDepartment of Veterinary Clinical and Life Sciences, College of Veterinary Medicine, Utah State University, Logan, UT, USA.ORCID 0000-0001-5673-3164
Evan K PetersonCenter for Integrated BioSystems, Utah State University, Logan, UT, USA.
Aaron J ThomasCenter for Integrated BioSystems, Utah State University, Logan, UT, USA.ORCID 0000-0002-6994-0338
Andrea L GilesDepartment of Veterinary Clinical and Life Sciences, College of Veterinary Medicine, Utah State University, Logan, UT, USA.
Young-Min LeeDepartment of Animal, Dairy and Veterinary Sciences, Quinney College of Agriculture and Natural Resources, Utah State University, Logan, UT, USA.ORCID 0000-0002-3974-3405
Irina A PolejaevaDepartment of Animal, Dairy and Veterinary Sciences, Quinney College of Agriculture and Natural Resources, Utah State University, Logan, UT, USA.ORCID 0000-0002-0858-5889
Heloisa M RutiglianoDepartment of Veterinary Clinical and Life Sciences, College of Veterinary Medicine, Utah State University, Logan, UT, USA.ORCID 0000-0003-2807-5007

Funding

Agriculture and Food Research Initiative Competitive 2021-67016-33504Agriculture and Food Research Initiative Competitive 2024-67016-42366USDA National Institute of Food and Agriculture
6 · The paper itself

Abstract

The effects of type I interferons, including interferon tau (IFNT), previously thought to be the signal for pregnancy recognition in ruminants, are mediated by the type I interferon receptor (IFNAR), a heterodimer comprised of IFNAR1 and IFNAR2. The genes encoding IFNAR were disrupted in fetal fibroblast cells using CRISPR/Cas9 and lambs were produced by somatic cell nuclear transfer (SCNT). Subsequently, a herd of IFNAR2+/- sheep was developed and used to produce IFNAR2-/- lambs. Functional knockout of IFNAR was confirmed by failure of fibroblast cell lines from IFNAR2-/- sheep to respond to interferon alpha or IFNT in a quantitative reverse-transcription polymerase chain reaction assay for interferon-stimulated gene expression. Wild-type cells respond robustly in this assay. Successful production of IFNAR2-/- lambs by SCNT demonstrated that the conceptus did not need to express IFNAR or respond to IFNT. Nevertheless, because the accepted paradigm suggested that IFNT was required for pregnancy recognition, we hypothesized that IFNAR2-/- ewes would be infertile. It was, therefore, surprising when two ~9-month-old IFNAR2-/- ewes bred to an IFNAR2+/- ram became pregnant and had normal pregnancies culminating in healthy lambs in May 2023. These pregnancies demonstrate that the IFNAR, and presumably IFNT, are not required for the establishment or normal progression of pregnancy. Since IFNAR-/- fetuses survive to term, and both IFNAR2-/- rams and ewes are fertile, unless there is another receptor for IFNT, which is unlikely, IFNT is not required for pregnancy recognition or the development of a healthy ruminant fetus.

Indexed as

Receptor, Interferon alpha-betaAnimalsAnimals, Genetically ModifiedFemaleGene Knockout TechniquesInterferon Type IPregnancyPregnancy ProteinsSheepinterferon tauInterferon Type IPregnancy ProteinsReceptor, Interferon alpha-betaCRISPR/Cas9interferon receptor knockoutinterferon taupregnancy recognitionsheep

Identifiers

PMID42261664
PMCPMC13482288

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.