A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells

Kwiatkowski DJ, Zhang H, Bandura JL, Heiberger KM, Glogauer M, el-Hashemite N, Onda H · 2002 · Human Molecular Genetics · Atlas ID KWI2002

What this study shows

The authors built a Tsc1 knockout mouse to model tuberous sclerosis. Embryos lacking both copies of Tsc1 died at mid-gestation because the liver failed to develop. Mice with one copy often developed kidney cystadenomas and liver hemangiomas; the hemangiomas were more common, more severe and more often fatal in females. Fibroblasts lacking Tsc1 showed persistent phosphorylation of S6K and its substrate S6 that rapamycin could reverse, and S6 phosphorylation was also high in kidney tumours from the mice. The authors suggested that blocking this pathway might help control TSC tumours. Boundary: mouse model and mouse cells; the rapamycin result is in cultured cells, and treatment of the mouse tumours was not tested here.

Abstract

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Tuberous sclerosis (TSC) is a autosomal dominant genetic disorder caused by mutations in either TSC1 or TSC2, and characterized by benign hamartoma growth. We developed a murine model of Tsc1 disease by gene targeting. Tsc1 null embryos die at mid-gestation from a failure of liver development. Tsc1 heterozygotes develop kidney cystadenomas and liver hemangiomas at high frequency, but the incidence of kidney tumors is somewhat lower than in Tsc2 heterozygote mice. Liver hemangiomas were more common, more severe and caused higher mortality in female than in male Tsc1 heterozygotes.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Tsc1 knockout mice (null embryos, heterozygotes); Tsc1-null mouse embryonic fibroblasts; rapamycin treatment of cells); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Tsc1 knockout mice (null embryos, heterozygotes); Tsc1-null mouse embryonic fibroblasts; rapamycin treatment of cells
Journal	Human Molecular Genetics
Year	2002
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1093/hmg/11.5.525 · PMID 11875047

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	Tsc1 gene targeting (null and heterozygous)
Target	Embryonic survival; kidney and liver tumours; S6K/S6 phosphorylation
Model	Mus musculus
Effect	Tsc1 loss -> embryonic lethality (null), tumours and female-biased mortality (heterozygotes), constitutive rapamycin-sensitive S6K activation

In the Atlas

Links in the pathway map

Supports TSC1/TSC2 inhibits mTORC1

Cite this paper

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Kwiatkowski, D. J., Zhang, H., Bandura, J. L., Heiberger, K. M., Glogauer, M., el-Hashemite, N., & Onda, H. (2002). A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Human Molecular Genetics. https://doi.org/10.1093/hmg/11.5.525

@article{KWI2002,
  author       = {Kwiatkowski, D. J. and Zhang, H. and Bandura, J. L. and Heiberger, K. M. and Glogauer, M. and el-Hashemite, N. and Onda, H.},
  title        = {{A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells}},
  journal      = {Human Molecular Genetics},
  year         = {2002},
  doi          = {10.1093/hmg/11.5.525},
  note         = {PMID: 11875047},
}

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 KWI2002) [Data set]. https://mtor-atlas.org/study/KWI2002/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_KWI2002,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record KWI2002},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/KWI2002/},
  doi          = {10.5281/zenodo.22059963}
}

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