Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice

Tsai PT, Hull C, Chu Y, Greene-Colozzi E, Sadowski AR, Leech JM, Steinberg J, Crawley JN, Regehr WG, Sahin M · 2012 · Nature · Atlas ID TSA2012

What this study shows

Deleting one or both copies of Tsc1 only in cerebellar Purkinje cells raised phospho-S6 (a readout of mTORC1) in those cells. Both heterozygous and homozygous mutants showed autism-like behaviour: no preference for a mouse over an object or for a new mouse, more self-grooming, more pup ultrasonic calls and poorer reversal learning in a water T-maze. Purkinje cells fired fewer action potentials, both spontaneously and when driven, in a gene-dose-dependent way, while their synaptic inputs looked largely normal; homozygous mutants also lost Purkinje cells from about 2 months of age and became ataxic. Rapamycin (6 mg/kg intraperitoneally, three times a week from postnatal day 7) prevented the Purkinje cell loss and enlargement and the social, learning and motor deficits. Boundary: mouse, cell-type-specific genetic deletion; rapamycin given from early postnatal life, so this is prevention, not reversal; relevance to human autism is by analogy with TSC patients.

Abstract

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Autism spectrum disorders (ASDs) are highly prevalent neurodevelopmental disorders, but the underlying pathogenesis remains poorly understood. Recent studies have implicated the cerebellum in these disorders, with post-mortem studies in ASD patients showing cerebellar Purkinje cell (PC) loss, and isolated cerebellar injury has been associated with a higher incidence of ASDs. However, the extent of cerebellar contribution to the pathogenesis of ASDs remains unclear.

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: L7Cre;Tsc1 flox mice (Purkinje-cell-specific heterozygous and homozygous Tsc1 deletion); cerebellar slice electrophysiology; behaviour; rapamycin from P7); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	L7Cre;Tsc1 flox mice (Purkinje-cell-specific heterozygous and homozygous Tsc1 deletion); cerebellar slice electrophysiology; behaviour; rapamycin from P7
Journal	Nature
Year	2012
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/nature11310 · PMID 22763451 · Free full text (PMC3615424)

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	Purkinje-cell-specific Tsc1 deletion; rapamycin
Target	TSC1/TSC2 -> mTORC1
Model	Mouse
Effect	Tsc1 loss in Purkinje cells caused autism-like behaviour and reduced PC excitability; rapamycin prevented the deficits

In the Atlas

Links in the pathway map

Supports TSC1/TSC2 inhibits mTORC1

Cite this paper

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Tsai, P. T., Hull, C., Chu, Y., Greene-Colozzi, E., Sadowski, A. R., Leech, J. M., Steinberg, J., Crawley, J. N., Regehr, W. G., & Sahin, M. (2012). Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature. https://doi.org/10.1038/nature11310

@article{TSA2012,
  author       = {Tsai, P. T. and Hull, C. and Chu, Y. and Greene-Colozzi, E. and Sadowski, A. R. and Leech, J. M. and Steinberg, J. and Crawley, J. N. and Regehr, W. G. and Sahin, M.},
  title        = {{Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice}},
  journal      = {Nature},
  year         = {2012},
  doi          = {10.1038/nature11310},
  note         = {PMID: 22763451},
}

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 TSA2012) [Data set]. https://mtor-atlas.org/study/TSA2012/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_TSA2012,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record TSA2012},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/TSA2012/},
  doi          = {10.5281/zenodo.22059963}
}

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