A patient-based murine model recapitulates human STAT3 gain-of-function syndrome Article Swipe
Kornvalee Meesilpavikkai
,
Zijun Zhou
,
Kasiphak Kaikaew
,
Suphattra Phakham
,
Peter J. van der Spek
,
Sigrid Swagemakers
,
Deon J. Venter
,
Maaike de Bie
,
Benjamin Schrijver
,
Christopher Schliehe
,
Fabian Kaiser
,
Virgil A. S. H. Dalm
,
P. Martin van Hagen
,
Nattiya Hirankarn
,
Hanna IJspeert
,
Willem A. Dik
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.clim.2024.110312
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.clim.2024.110312
STAT3 gain-of-function (GOF) variants results in a heterogeneous clinical syndrome characterized by early onset immunodeficiency, multi-organ autoimmunity, and lymphoproliferation. While 191 documented cases with STAT3 GOF variants have been reported, the impact of individual variants on immune regulation and the broad clinical spectrum remains unclear. We developed a Stat3p.L387R mouse model, mirroring a variant identified in a family exhibiting common STAT3 GOF symptoms, and rare phenotypes including pulmonary hypertension and retinal vasculitis. In vitro experiments revealed increased STAT3 phosphorylation, nuclear migration, and DNA binding of the variant. Our Stat3p.L387R model displayed similar traits from previous Stat3GOF strains, such as splenomegaly and lymphadenopathy. Notably, Stat3p.L387R/+ mice exhibited heightened embryonic lethality compared to prior Stat3GOF/+ models and ocular abnormalities were observed. This research underscores the variant-specific pathology in Stat3p.L387R/+ mice, highlighting the ability to recapitulate human STAT3 GOF syndrome in patient-specific transgenic murine models. Additionally, such models could facilitate tailored treatment development.
Related Topics
Concepts
Gain of function
Function (biology)
STAT3
Medicine
Cell biology
Biology
Signal transduction
Genetics
Mutation
Gene
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.clim.2024.110312
- OA Status
- hybrid
- Cited By
- 3
- References
- 48
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4400664157
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4400664157Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1016/j.clim.2024.110312Digital Object Identifier
- Title
-
A patient-based murine model recapitulates human STAT3 gain-of-function syndromeWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-07-15Full publication date if available
- Authors
-
Kornvalee Meesilpavikkai, Zijun Zhou, Kasiphak Kaikaew, Suphattra Phakham, Peter J. van der Spek, Sigrid Swagemakers, Deon J. Venter, Maaike de Bie, Benjamin Schrijver, Christopher Schliehe, Fabian Kaiser, Virgil A. S. H. Dalm, P. Martin van Hagen, Nattiya Hirankarn, Hanna IJspeert, Willem A. DikList of authors in order
- Landing page
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https://doi.org/10.1016/j.clim.2024.110312Publisher landing page
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://doi.org/10.1016/j.clim.2024.110312Direct OA link when available
- Concepts
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Gain of function, Function (biology), STAT3, Medicine, Cell biology, Biology, Signal transduction, Genetics, Mutation, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
3Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 1Per-year citation counts (last 5 years)
- References (count)
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48Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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