Molecular cloning and characterization of a mouse nuclear orphan receptor expressed in embryos and testes.
A mouse cDNA encoding a putative DNA-binding protein of the zinc-finger type was isolated from an E8.5 mouse embryonic cDNA library. Sequence comparison revealed a high degree of homology between this mouse cDNA and the human and rat orphan receptor Tr2-11 isolated from prostate cDNA libraries. This transcript was detected in early-to-midgestation embryos and was seen to level off during later stages of development. In adult animals, a high level of expression was detected only in the testis, starting at postnatal day 18, a stage when active meiosis begins to occur. A specific antibody was raised, and immunoreactive signal was specifically located in the adlumenal compartment of the seminiferous tubule, where advanced germ cells reside. In mice fed a vitamin A-depleted diet, where the testes were depleted of advanced germ cells, expression of this protein could not be detected, suggesting a biological relation of this orphan receptor and male germ-cell differentiation. Using a retinoic acid response element (RARE)-containing reporter system, it was demonstrated that expression of this protein dramatically repressed both the basal and the retinoic acid (RA)-regulated promoter activities of this reporter. Thus, this orphan receptor could play a role in modulating both the basic transcription machinery and the RA signalling pathway during embryogenesis and male germ-cell differentiation.
Lee
C H
CH
Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA.
Chang
L
L
Wei
L N
LN
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001483:Base Sequence; D015152:Blotting, Northern; D019556:COS Cells; D003001:Cloning, Molecular; D018076:DNA, Complementary; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008297:Male; D051379:Mice / Q000196:embryology; D008969:Molecular Sequence Data; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics*; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000378:metabolism*; D014018:Tissue Distribution; D014802:Vitamin A Deficiency
D000906:Antibodies; D018076:DNA, Complementary; C539822:NR2C1 protein, human; C539823:Nr2c1 protein, mouse; C539824:Nr2c1 protein, rat; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D008156:Luciferases