Abstract
We show that mice expressing retinoid X receptor beta (RXRbeta) impaired in its transcriptional activation function AF-2 (Rxrb(af20) mutation) do not display the spermatid release defects observed in RXRbeta-null mutants, indicating that the role of RXRbeta in spermatid release is ligand-independent. In contrast, like RXRbeta-null mutants, Rxrb(af20) mice accumulate cholesteryl esters in Sertoli cells (SCs) due to reduced ABCA1 transporter-mediated cholesterol efflux. We provide genetic and molecular evidence that cholesterol homeostasis in SCs does not require PPARalpha and beta, but depends upon the TIF2 coactivator and RXRbeta/LXRbeta heterodimers, in which RXRbeta AF-2 is transcriptionally active. Our results also indicate that RXRbeta may be activated by a ligand distinct from 9-cis retinoic acid.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Animals
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Cholesterol / metabolism*
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DNA-Binding Proteins
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Dimerization
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Electrophoretic Mobility Shift Assay
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Gene Expression Regulation
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Gene Silencing
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Histone Acetyltransferases
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Homeostasis
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Immunochemistry
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Ligands
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Liver X Receptors
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Male
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Mice
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Mice, Knockout
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Nuclear Receptor Coactivator 1
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Nuclear Receptor Coactivator 2
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Orphan Nuclear Receptors
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Protein Binding
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism
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Retinoid X Receptor beta / genetics
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Retinoid X Receptor beta / metabolism*
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Sertoli Cells / metabolism*
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Sertoli Cells / physiology
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Spermatids / cytology
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Spermatids / physiology
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Transcription Factors / metabolism
Substances
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ATP-Binding Cassette Transporters
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DNA-Binding Proteins
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Ligands
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Liver X Receptors
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Ncoa2 protein, mouse
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Nuclear Receptor Coactivator 2
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Orphan Nuclear Receptors
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Receptors, Cytoplasmic and Nuclear
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Retinoid X Receptor beta
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Transcription Factors
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Cholesterol
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Histone Acetyltransferases
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Ncoa1 protein, mouse
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Nuclear Receptor Coactivator 1