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TSC2-Mutant Yucatan Minipig Cardiac Rhabdomyoma Model Reveals mTORC1 Activation and MITF/TFE Expression Signature

Bou Farhat E, Du H, Carreon CK, Halawi J, Kudler S, Losko M, Herbert ZT, Watson AL, Carlson D, Webster DA, Korpela DM, …, Kwiatkowski DJ · 2026 · JCI Insight · Atlas ID BOU2026

What this study shows

A heterozygous TSC2 p.Arg505\* minipig developed cardiac rhabdomyomas resembling the human lesions, with mTORC1 signalling activation and an MITF/TFE-regulated lysosomal gene signature shared with human tumours. Animal model only; other TSC manifestations were not seen up to one year of age.

Abstract

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Tuberous sclerosis complex (TSC) is an inherited tumor predisposition syndrome caused by pathogenic variants in TSC1 or TSC2, yet no animal model faithfully recapitulates the cardiac rhabdomyomas (CR) that are among its earliest manifestations. We generated a heterozygous TSC2-mutant Yucatan minipig carrying the recurrent pathogenic TSC2 p.Arg505* variant and characterized its cardiac phenotype using histopathology, immunohistochemistry, and RNA sequencing.

Read the full abstract on PubMed →

At a glance

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Evidence type A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Heterozygous TSC2-mutant Yucatan minipig (p.Arg505*)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type4 - Animal Study
Model systemHeterozygous TSC2-mutant Yucatan minipig (p.Arg505*)
JournalJCI Insight
Year2026
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1172/jci.insight.211025 · PMID 42986687

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

People in the Atlas

  • Elias Bou Farhat first author · 1 study in the Atlas

    First author of the 2026 JCI Insight paper on a TSC2-mutant minipig model of cardiac rhabdomyoma.

  • David J. Kwiatkowski last author · 7 studies in the Atlas

    Geneticist and physician who studies tuberous sclerosis complex (TSC) and the TSC1/TSC2 genes that restrain mTORC1.

  • Elizabeth P Henske 2 studies in the Atlas

    Tuberous sclerosis researcher and co-author of the 2026 TSC2 minipig study and the 2017 Cancer Cell paper on mTORC1 and nucleotide synthesis.

More: 11 other authors

No profile yet: Du H, Carreon CK, Halawi J, Kudler S, Losko M, Herbert ZT, Watson AL, Carlson D, Webster DA, Korpela DM, Meredith DM

Related studies

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Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

InterventionGenetic (TSC2 p.Arg505* heterozygous mutation)
TargetTSC2 / mTORC1 / MITF-TFE
ModelYucatan minipig (Sus scrofa)
EffectTSC2-mutant minipigs develop cardiac rhabdomyomas with mTORC1 activation and an MITF/TFE lysosomal signature

Cite this paper

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Bou Farhat, E., Du, H., Carreon, C. K., Halawi, J., Kudler, S., Losko, M., Herbert, Z. T., Watson, A. L., Carlson, D., Webster, D. A., Korpela, D. M., Meredith, D. M., Henske, E. P., & Kwiatkowski, D. J. (2026). TSC2-Mutant Yucatan Minipig Cardiac Rhabdomyoma Model Reveals mTORC1 Activation and MITF/TFE Expression Signature. JCI Insight. https://doi.org/10.1172/jci.insight.211025

@article{BOU2026,
  author       = {Bou Farhat, E. and Du, H. and Carreon, C. K. and Halawi, J. and Kudler, S. and Losko, M. and Herbert, Z. T. and Watson, A. L. and Carlson, D. and Webster, D. A. and Korpela, D. M. and Meredith, D. M. and Henske, E. P. and Kwiatkowski, D. J.},
  title        = {{TSC2-Mutant Yucatan Minipig Cardiac Rhabdomyoma Model Reveals mTORC1 Activation and MITF/TFE Expression Signature}},
  journal      = {JCI Insight},
  year         = {2026},
  doi          = {10.1172/jci.insight.211025},
  note         = {PMID: 42986687},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record BOU2026) [Data set]. https://mtor-atlas.org/study/BOU2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_BOU2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record BOU2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/BOU2026/},
  doi          = {10.5281/zenodo.22059963}
}
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