Evidence map›Paper›PMID 39756463›Full record

ArticleInflammatory bowel diseases2025

A Similar Mutation in the AAUU-Rich Elements of the Mouse TNF Gene Results in a Distinct Ileocolitic Phenotype: A New Strain of TNF-Overexpressing Mice.

Amruth Chilukuri, Margaret Kim, Taniya Mitra, John M Gubatan, Josef Urrete, Leo D Saxon, Amber Ablack, Zbigniew Mikulski, Katarzyna Dobaczewska, Zining Shen and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Inflammatory bowel diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

20 authors.

Amruth ChilukuriDivision of Gastroenterology, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-7019-2541
Margaret KimDivision of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
Taniya MitraDivision of Gastroenterology, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0003-0214-0755
John M GubatanDivision of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-6037-2883
Josef UrreteDivision of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
Leo D SaxonDivision of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
Amber AblackDivision of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
Zbigniew MikulskiMicroscopy and Histology Core, La Jolla Institute of Allergy and Immunology, La Jolla, CA, USA.ORCID 0000-0002-1964-6528
Katarzyna DobaczewskaMicroscopy and Histology Core, La Jolla Institute of Allergy and Immunology, La Jolla, CA, USA.ORCID 0000-0002-6377-018X
Zining ShenDivision of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
Mary KeirGenentech Pharmaceuticals, South San Francisco, CA, USA.ORCID 0000-0002-0637-4092
Tangsheng YiGenentech Pharmaceuticals, South San Francisco, CA, USA.ORCID 0000-0002-2959-4979
Prabhdeep KaurDivision of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
Patricia OliveiraRheumatology Division, University of California San Diego, La Jolla, CA, USA.
Jessica Murillo-SaichRheumatology Division, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-1169-2888
Eric Y ChangRadiology Department, San Diego VA Medical Center, La Jolla Village Drive, San Diego, CA, USA.ORCID 0000-0003-3633-5630
Calen A SteinerDivision of Gastroenterology, University of Colorado, Denver, CO, USA.ORCID 0000-0002-1964-010X
Paul JedlickaDepartment of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.ORCID 0000-0001-7839-6912
Mónica GumaRheumatology Division, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0003-1951-9411
Jesús Rivera-NievesDivision of Gastroenterology, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-7887-7959

Funding

San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8M
HIV Persistence and Renewal in the Gastrointestinal, Genitourinary and Adipose TissuesR01DK131532 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RIVERA-NIEVES, JESUS, SMITH, DAVID MITCHELL · 2021 to 2025
$3.9M
Rheumatic Diseases Research Training GrantT32AR064194 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GARY S FIRESTEIN, Monica Guma · 2013 to 2026
$3.8M
Integrin αEβ7-dependent IgA transcytosis during homeostasis and IBDR01DK132242 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesus Rivera-Nieves · 2022 to 2026
$2.6M
Enhancing Mentoring of Diverse Early Career ResearchersK26DK138378 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesus Rivera-Nieves · 2023 to 2026
$448k
Immunoprofiling for identifying biomarkers in celiac diseaseR21AI149636 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ERNST, PETER B., RIVERA-NIEVES, JESUS · 2020 to 2021
$433k
The role of Axl signaling in intestinal fibrosisK08DK138279 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Calen Andrew Steiner · 2025 to 2026
$328k
BLRD VA I01 BX005951NIAID NIH HHS R21 AI149636NIAMS NIH HHS T32 AR064194NIDDK NIH HHS K08 DK138279NIDDK NIH HHS K26 DK138378NIDDK NIH HHS P30 DK120515NIDDK NIH HHS R01 DK131532NIDDK NIH HHS R01 DK132242NIH HHS R01DK32242VA Merit BLRD-I01 BX005951
6 · The paper itself

Abstract

backgroundTumor necrosis factor (TNF) is a pleiotropic cytokine that plays a critical role in the pathogenesis of immune-mediated diseases including inflammatory bowel disease (IBD). The stability of its mRNA transcript, determined in part by destabilizing sequences in its AAUU repeats (ARE) gene region, is an important regulator of its tissue and systemic levels. A deletion in the ARE region of the gene resulted in IBD and arthritis in mice and pigs, supporting a critical role for the cytokine in human IBD and several human arthritides. A mutation in the same area of the mouse genome by Genentech scientists (T.Y., M.K.) resulted in a similar but not identical phenotype.

methodsHere, we compare histopathological, cellular, and molecular features of the strains and propose reasons for their distinct phenotypes. First, while homozygous TNFΔARE mice develop severe arthritis and die after weaning, homozygous Genentech TNFΔARE (ΔG/ΔG) mice have normal lifespans, and males are often fertile.

resultsWe found that while the ileitic phenotype had peaked at 12 weeks of age in all mice, colitis progressed mostly after 20 weeks of age in heterozygous mice. Their variably penetrant arthritic phenotype progressed mostly after 20 weeks, also in heterozygous mice from both strains. There was expansion of central memory T and B cells in lymphoid organs of TNF-overproducing strains and their transcriptional profile shared well-known pathogenetic pathways with human IBD. Finally, we found differences in the mutated sequences within the ARE regions of the TNF gene and in their microbiota composition and genetic background. These differences likely explain their phenotypic differences.

conclusionsIn summary, we describe a different strain of TNF-overproducing mice with an overlapping, yet not identical phenotype, which may have differential applications than the original strain.

Indexed as

ColitisMutationTumor Necrosis Factor-alphaAnimalsDisease Models, AnimalFemaleMaleMiceMice, Inbred C57BLPhenotypeTnf protein, mouseTumor Necrosis Factor-alphaarthritisIBD mouse modelsileitistranscriptomicstumor necrosis factor

Identifiers

PMID39756463
PMCPMC11985683

What OpenQuestion holds

Textmetadata
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.