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Disruption of the nuclear hormone receptor RORα in staggerer mice

Nature volume 379, pages 736–739 (1996)Cite this article

A Correction to this article was published on 23 May 1996

Abstract

HOMOZYGOUS staggerer (sg) mice show a characteristic severe cerebellar ataxia due to a cell-autonomous defect in the development of Purkinje cells1,2. These cells show immature morphology, synaptic arrangement, biochemical properties and gene expression, and are reduced in numbers3–12. In addition, sg heterozygotes show accelerated dendritic atrophy and cell loss13, suggesting that sg has a role in mature Purkinje cells. Effects of this mutation on cerebellar development have been studied for 25 years, but its molecular basis has remained unknown. We have genetically mapped staggerer to an interval of 160 kilobases on mouse chromosome 9 which was found to contain the gene encoding RORα, a member of the nuclear hormone-receptor superfamily. Staggerer mice were found to carry a deletion within the RORα gene that prevents translation of the ligand-binding homology domain. We propose a model based on these results, in which RORα interacts with the thyroid hormone signalling pathway to induce Purkinje-cell maturation.

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Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, Nine Cambridge Centre, Cambridge, Massachusetts, 02142, USA

    Bruce A. Hamilton, Anne W. Kerrebrock, Trevor L. Hawkins, William FitzHugh, Kenro Kusumi, Ken L. Mueller, Victor van Berkel, Bruce W. Birren, Leonid Kruglyak & Eric S. Lander

  2. The Jackson Laboratory, Bar Harbor, Maine, 04609, USA

    Wayne N. Frankel

  3. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    Kenro Kusumi & Eric S. Lander

  4. Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, 37831-8077, USA

    Liane B. Russell

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  1. Bruce A. Hamilton
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Hamilton, B., Frankel, W., Kerrebrock, A. et al. Disruption of the nuclear hormone receptor RORα in staggerer mice. Nature 379, 736–739 (1996). https://doi.org/10.1038/379736a0

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