MOLECULAR-CLONING OF OVINE AND BOVINE TYPE-I INTERFERON RECEPTOR SUBUNITS FROM UTERI, AND ENDOMETRIAL EXPRESSION OF MESSENGER-RIBONUCLEIC-ACID FOR OVINE RECEPTORS DURING THE ESTROUS-CYCLE AND PREGNANCY

Interferon-tau (IFN-tau), a type I IFN structurally related to IFN-alp ha, is regarded as the major antiluteolytic factor secreted by the con ceptus of ruminant ungulate species before definitive trophoblast atta chment and implantation. It mediates its effects by acting on the uter ine endometrium, where it blunts the normal pulsatile production of PG F(2) alpha, presumably as a result of its binding to type I IFN recept ors. In this study, we describe the complementary DNAs for the two kno wn subunits, IFNAR1 and IFNAR2, of this receptor isolated from bovine and ovine endometrial complementary DNA libraries by homology cloning. Although there is extensive inferred amino acid sequence similarity b etween bovine and ovine IFNAR1 (92% identity) and between bovine and o vine IFNAR2 (88% identity), they have diverged extensively from the hu man receptor subunits (similar to 67% and similar to 58% identity, res pectively). Despite these differences in primary structure, the respec tive subunits from all three species are organized similarly in their extracellular and cytoplasmic regions, and the bovine and ovine subuni ts have each retained a number of polypeptide motifs implicated in sig nal transduction. These uterine receptors also ay,pear not to be splic e variants. The cloned ovine IFNAR1 subunit, for example, possesses th e expected four extracellular SD100 domains of full-length bovine and huIFNAR1, and only the homologs of the so-called long form (huIFNAR2c) of human IFNAR2 have so far been identifed. RT-PCR procedures indicat e that the messenger RNA for both subunits are found, not only in endo metrium, but in all other tissues examined except those of preimplanta tion conceptuses, which presumably cannot respond to the IFN-tau they produce. Quantitative RNase protection assays of ovine endometrial RNA show that the expression of neither subunit changes greatly during th e estrous cycle or pregnancy. These data suggest that the type I IFN r eceptor, which is expressed by the endometrium and binds IFN-tau, is p robably not a structurally unusual form.