TSC2-Mutant Yucatan Minipig Cardiac Rhabdomyoma Model Reveals mTORC1 Activation and MITF/TFE Expression Signature
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 type | 4 - Animal Study |
| Model system | Heterozygous TSC2-mutant Yucatan minipig (p.Arg505*) |
| Journal | JCI Insight |
| Year | 2026 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 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
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First author of the 2026 JCI Insight paper on a TSC2-mutant minipig model of cardiac rhabdomyoma.
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Geneticist and physician who studies tuberous sclerosis complex (TSC) and the TSC1/TSC2 genes that restrain mTORC1.
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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
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Topics
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.
| Intervention | Genetic (TSC2 p.Arg505* heterozygous mutation) |
| Target | TSC2 / mTORC1 / MITF-TFE |
| Model | Yucatan minipig (Sus scrofa) |
| Effect | TSC2-mutant minipigs develop cardiac rhabdomyomas with mTORC1 activation and an MITF/TFE lysosomal signature |
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