Faculty Research 1990 - 1999
Disruption of the nuclear hormone receptor RORalpha in staggerer mice.
Document Type
Article
Publication Date
1996
Keywords
Animal, Base-Sequence, Brain: em, cy, me, Cell-Differentiation: ph, Cerebellar-Ataxia: ge, Chromosome-Mapping, DNA-Binding-Proteins: ge, ph, DNA-Complementary, Female, Male, Mice, Mice-Inbred-C57BL, Mice-Neurologic-Mutants: ge, Molecular-Sequence-Data, Polymerase-Chain-Reaction, Purkinje-Cells: pa, Receptors-Cell-Surface: ge, ph, Receptors-Cytoplasmic-and-Nuclear: ge, ph, SUPPORT-U-S-GOVT-P-H-S, Trans-Activators: ge, ph
First Page
736
Last Page
739
JAX Source
Nature 1996 Feb 22;379(6567):736-9
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 RORalpha, a member of the nuclear hormone-receptor superfamily. Staggerer mice were found to carry a deletion within the RORalpha gene that prevents translation of the ligand-binding homology domain. We propose a model based on these results, in which RORalpha interacts with the thyroid hormone signalling pathway to induce Purkinje-cell maturation.
Recommended Citation
Hamilton BA,
Frankel WN,
Kerrebrock AW,
Hawkins TL,
FitzHugh W,
Kusumi K,
Russell LB,
Mueller KL,
van Be,
Birren BW,
Kruglyak L,
Lander ES.
Disruption of the nuclear hormone receptor RORalpha in staggerer mice. Nature 1996 Feb 22;379(6567):736-9