Disruption of the nuclear hormone receptor RORα in staggerer mice

Bruce A. Hamilton, Wayne N. Frankel, Anne W. Kerrebrock, Trevor L. Hawkins, William FitzHugh, Kenro Kusumi, Liane B. Russell, Ken L. Mueller, Victor Van Berkel, Bruce W. Birren, Leonid Kruglyak, Eric S. Lander

Research output: Contribution to journalArticlepeer-review

399 Scopus citations

Abstract

Homozygous staggerer (sg) mice show a characteristic severe cerebellar ataxia due to a cell-autonomous defect in the development of Purkinje cells. These cells show immature morphology, synaptic arrangement, biochemical properties and gene expression, and are reduced in numbers. In addition, sg heterozygotes show accelerated dendritic atrophy and cell loss, 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.

Original languageEnglish (US)
Pages (from-to)736-739
Number of pages4
JournalNature
Volume379
Issue number6567
DOIs
StatePublished - Feb 22 1996
Externally publishedYes

ASJC Scopus subject areas

  • General

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