Different ovine interferon-tau genes are not expressed identically and their protein products display different activities

Interferon tau (IFN-tau) proteins are secreted by the ovine conceptus for a few days before definitive attachment of the trophoblast to the uterine epithelium and act to prolong luteal life span. Multiple genes encode for IFN-tau in sheep, but it remains unclear which genes are expressed during early pregnancy and whether the proteins encoded by these genes are equipotent. Three distinct ovine (ov) IFN-tau gene variants, p3, p6, and s4, were examined to determine whether they differed in gene expression and whether the proteins displayed different biological activities. By using RNase protection assays, full- length protected fragments were detected for p3 and p6 in approximately similar proportions in conceptuses flushed from the uterus at Days 12- 13, Days 15-16, and Days 18-19 of pregnancy, but the amount of full- length protected s4 transcripts was 10% to 20% of that for p3 and p6. Partially protected probe fragments were also evident, presumably from probe hybridization to related ovIFN-tau transcripts. Recombinant proteins were generated and exhibited 34.2 (p3), 8.4 (p6), and 11.9 (s4) units (x 10(-7)) of activity per milligram of protein when tested on MadinDarby bovine kidney cells. Antiproliferative activity on human Daudi cells varied considerably between the interferons, with p3 being 2000-fold more potent than s4. The interferons were injected into the uterine lumen of ewes from 10 to 18 days postestrus. The functional life span of the corpus luteum (CL) was increased (p = 0.02) by either 300 microg/day p3 (31.7 +/- 7.8 days) or 300 microg/day p6 (25.5 +/- 4.2 days), but not by 300 microg/day s4 (19.2 +/- 2.9 days), when compared to controls (15.8 +/- 0.6 days). Injection of 1 mg/day s4 did, however, increase (p = 0.02) CL life span (23.5 +/- 4.1 days). These data suggest that IFN-tau genes are not equally expressed in trophectoderm and that ovIFN-tau genes encode for proteins with significantly different biological potency.