Evidence map›Paper›PMID 36156081›Full record

ArticleEndocrinology2022

Foxe1 Deletion in the Adult Mouse Is Associated With Increased Thyroidal Mast Cells and Hypothyroidism.

Grace Lim, Alexander Widiapradja, Scott P Levick, Kelly J McKelvey, Xiao-Hui Liao, Samuel Refetoff, Martyn Bullock, Roderick J Clifton-Bligh

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 35% of its field
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

8 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
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  5. foxe1 mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations.Developmental dynamics : an official publication of the American Association of Anatomists · 2025
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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

8 authors at 2 institutions in 2 countries.

Grace LimCancer Genetics Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, St Leonards, NSW 2065, Australia.
Alexander WidiapradjaCardiac Biology and Heart Failure Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, St Leonards, NSW 2065, Australia.
Scott P LevickCardiac Biology and Heart Failure Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, St Leonards, NSW 2065, Australia.
Kelly J McKelveyBill Walsh Translational Cancer Research Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, St Leonards, NSW 2065, Australia.
Xiao-Hui LiaoDepartment of Medicine, The University of Chicago, Chicago, Illinois 60637, USA.
Samuel RefetoffDepartment of Medicine, Pediatrics and Committee on Genetics, The University of Chicago, Chicago, Illinois 60637, USA.
Martyn BullockCancer Genetics Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, St Leonards, NSW 2065, Australia.ORCID 0000-0002-3740-5509
Roderick J Clifton-BlighCancer Genetics Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, St Leonards, NSW 2065, Australia.
The University of Sydney · AUUniversity of Chicago · US

Funding

THYROID PHYSIOLOGY STUDIES OF INHERITED DISORDERSR01DK015070 · NIDDK · UNIVERSITY OF CHICAGO · PI ANTONIO C BIANCO, Alexandra Mihaela Dumitrescu · 1986 to 2026
$8.1M
NIDDK NIH HHS R01 DK015070
6 · The paper itself

Abstract

contextFoxe1 is a key thyroid developmental transcription factor. Germline deletion results in athyreosis and congenital hypothyroidism. Some data suggest an ongoing role for maintaining thyroid differentiation.

objectiveWe created a mouse model to directly examine the role of Foxe1 in the adult thyroid.

methodsA model of tamoxifen-inducible Cre-mediated ubiquitous deletion of Foxe1 was generated in mice of C57BL/6J background (Foxe1flox/flox/Cre-TAM). Tamoxifen or vehicle was administered to Foxe1flox/flox/Cre mice aged 6-8 weeks. Blood was collected at 4, 12, and 20 weeks, and tissues after 12 or 20 weeks for molecular and histological analyses. Plasma total thyroxine (T4), triiodothyronine, and thyrotropin (TSH) were measured. Transcriptomics was performed using microarray or RNA-seq and validated by reverse transcription quantitative polymerase chain reaction.

resultsFoxe1 was decreased by approximately 80% in Foxe1flox/flox/Cre-TAM mice and confirmed by immunohistochemistry. Foxe1 deletion was associated with abnormal follicular architecture and smaller follicle size at 12 and 20 weeks. Plasma TSH was elevated in Foxe1flox/flox/Cre-TAM mice as early as 4 weeks and T4 was lower in pooled samples from 12 and 20 weeks. Foxe1 deletion was also associated with an increase in thyroidal mast cells. Transcriptomic analyses found decreased Tpo and Tg and upregulated mast cell markers Mcpt4 and Ctsg in Foxe1flox/flox/Cre-TAM mice.

conclusionFoxe1 deletion in adult mice was associated with disruption in thyroid follicular architecture accompanied by biochemical hypothyroidism, confirming its role in maintenance of thyroid differentiation. An unanticipated finding was an increase in thyroidal mast cells. These data suggest a possible explanation for previous human genetic studies associating alleles in/near FOXE1 with hypothyroidism and/or autoimmune thyroiditis.

Indexed as

Congenital HypothyroidismMast CellsAnimalsCathepsin GForkhead Transcription FactorsMiceMice, Inbred C57BLTamoxifenThyrotropinThyroxineCathepsin GCtsg protein, mouseForkhead Transcription FactorsFOXE1 protein, humanFoxe1 protein, mouseTamoxifenThyrotropinThyroxineautoimmune thyroiditisFOXE1hypothyroidismmast cells

Identifiers

PMID36156081
PMCPMC9618408
OpenAlexW4297265113

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.