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Impaired extrapyramidal function caused by the targeted disruption of Retinoid X receptor RXRγ1 isoform
Author(s) -
Saga Yumiko,
Kobayashi Masahiko,
Ohta Hisashi,
Murai Naomi,
Nakai Nami,
Oshima Masanobu,
Taketo Makoto M.
Publication year - 1999
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.1999.00253.x
Subject(s) - biology , choline acetyltransferase , gene isoform , striatum , retinoid x receptor , receptor , cholinergic , dopamine , retinoid , microbiology and biotechnology , medicine , endocrinology , nuclear receptor , neuroscience , genetics , gene , retinoic acid , transcription factor
Background Retinoid X receptors RXRα, β and γ exert multiple functions in the genetic regulation of mammalian signalling systems by forming heterodimeric complexes with several nuclear ligand receptors. In contrast to the widespread expression of RXRα and RXRβ, the expression of RXRγ is restricted to particular tissues in which RXRγ1 is the major isoform expressed in the mouse corpus striatum. Results To investigate the function of this particular isoform RXRγ1, we generated RXRγ1 gene‐knockout mice by homologous recombination in ES cells. Both heterozygous and homozygous mice showed severe runting after birth, which often resulted in the early death of mice of the 129/C57BL‐6 genetic background. Independent of genetic background, however, the expression of choline acetyltransferase (ChAT) in the cholinergic interneurones in the striatum (caudal putamen) was markedly reduced in the RXRγ1 gene‐null mice. Furthermore, the mutant exhibited an altered response to the administration of dopamine receptor antagonists, haloperidol and chlorpromazine, which normally induce catalepsy in mice. Conclusions These results strongly suggest that RXRγ1 plays an important role in either the development or activation of cholinergic neurones in nigrostriatal extrapyramidal pathways.