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 signaling pathway during embryogenesis and male germ cell differentiation.