CoChat
Sign Up
Cited by 1,967TGF-β signaling in diseasesT-cell and B-cell ImmunologyPsoriasis: Treatment and Pathogenesis

Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death.

Open access
Kulkarni, A B, Huh, C G, Becker, D, Geiser, A, Lyght, M, Flanders, K C, Roberts, A B, Sporn, M B +2 more·1993·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.90.2.770PMC PMC45747
Open this paper in CoChat — free account

Abstract

To delineate specific developmental roles of transforming growth factor beta 1 (TGF-beta 1) we have disrupted its cognate gene in mouse embryonic stem cells by homologous recombination to generate TGF-beta 1 null mice. These mice do not produce detectable amounts of either TGF-beta 1 RNA or protein. After normal growth for the first 2 weeks they develop a rapid wasting syndrome and die by 3-4 weeks of age. Pathological examination revealed an excessive inflammatory response with massive infiltration of lymphocytes and macrophages in many organs, but primarily in heart and lungs. Many lesions resembled those found in autoimmune disorders, graft-vs.-host disease, or certain viral diseases. This phenotype suggests a prominent role for TGF-beta 1 in homeostatic regulation of immune cell proliferation and extravasation into tissues.

Integrity signals

Registry

Crossref · 10.1073/pnas.90.2.770

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • TGF-β1−/− mice are not viable on a 100% C57BL6 background.

    “Because TGF-β1−/− mice are not viable on a 100% C57BL6 background29, we refrained from backcrossing them.”

    From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [29]

  • TGF-β1−/− mice develop a lethal autoinflammatory syndrome shortly after birth linked to a T-cell specific deficiency of TGF-β.

    “TGF-β1−/− mice develop a lethal autoinflammatory syndrome shortly after birth29,30 which is linked to a T-cell specific deficiency of TGF-β31.”

    From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [29]

  • On the C57BL6/Sv129 background, 60-80% of homozygous TGF-β1−/− conceptuses reached parturition.

    “On the C57BL6/Sv129 background, 60–80% of (statistically expected) homozygous TGF-β1−/− conceptuses reached parturition as described29.”

    From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [29]

  • Key roles of TGF-β1 in suppressing the adaptive immune system are apparent from the lymphoproliferative autoimmune phenotype of Tgfb1−/− mice and similar phenotypes following selective ablation of TGF-β signaling components within CD4+ and CD8+ T cells.

    “Key roles of TGF-β1 in suppressing the adaptive immune system are apparent from the lymphoproliferative autoimmune phenotype of Tgfb1−/− mice197–199, and similar phenotypes following selective ablation of TGF-β signaling components within CD4+ and CD8+ T cells200.”

    From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [200]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Kulkarni, A. B., Huh, C. G., Becker, D., Geiser, A., Lyght, M., Flanders, K. C., Roberts, A. B., Sporn, M. B., Ward, J. M., & Karlsson, S.
Affiliations
National Institutes of Health (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1993-01-15
Volume
90
Issue
2
Pages
770-774
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.90.2.770
PMC
PMC45747
OpenAlex
W2079517510
Cited by
1,967
References
32
Citations by year
2026: 18 · 2025: 24 · 2024: 71 · 2023: 35 · 2022: 39 · 2021: 57 · 2020: 39 · 2019: 42 · 2018: 45 · 2017: 56 · 2016: 49 · 2015: 50 · 2014: 46 · 2013: 65 · 2012: 63
FWCI
20.24
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
TGF-β1, gene knockout, lymphocyte infiltration, macrophage infiltration, inflammation, cachexia, early mortality, heart, lung, immune homeostasis, immune cell proliferation, immune cell extravasation, autoimmune disease, graft-versus-host disease
MeSH terms
Alleles, Animals, Base Sequence, Embryo, Mammalian, Inflammation, Lung, Mice, Mutant Strains, Molecular Sequence Data, Mutation, Myocardium, Phenotype, Recombinant Fusion Proteins, Syndrome, Transformation, Genetic, Transforming Growth Factor beta, Leukemic Infiltration, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review