Biomedical subjects

R M Roberts

Publications and source records attributed to R M Roberts.

At least 91 records · Page 5Linked to original sources

PubMed1994

Interferon-tau and interferon-alpha interact with the same receptors in bovine endometrium. Use of a readily iodinatable form of recombinant interferon-tau for binding studies.

Trophoblasts of ruminant species secrete multiple forms of a novel Type I interferon (IFN-tau) for a few days preceding implantation. These IFN-tau are structurally distinct from IFN-alpha, -beta, and -omega, but it remains unclear whether they have any distinguishing biological properties. It has been of interest, therefore, to study their interaction with Type I IFN receptors. However, a recombinant bovine IFN-tau (boIFN-tau 1) prepared for such use is rapidly inactivated during chemical iodination with 125I, presumably because a critical tyrosine becomes modified. Here we describe the synthesis of a novel IFN-tau 1 in which Leu169 and Leu171 in the carboxyl terminus have been replaced by 2 tyrosine residues. The recombinant product (rboIFN-tau 1Y2) can be readily iodinated without significant loss of antiviral and antiproliferative activities, provided that reaction time with 125I is minimized. Both rboIFN-tau 1Y2 and rboIFN-alpha 1 compete with each other for binding to bovine endometrial cell membranes and Madin-Darby bovine kidney cells. Dissociation constants of both IFN are quite similar (Kd = 3.7 x 10(-10) and 3.5 x 10(-10) M, respectively). Cross-linking studies reveal a single size class of receptor polypeptide on endometrium and Madin-Darby canine kidney cells whose molecular weight is reduced from approximately 130,000 to approximately 70,000 by treatment with N-glycosidase. These studies with a single recombinant form of boIFN-tau avoid the difficulties that arise from use of a mixture of naturally occurring isoforms. They provide further evidence for the presence of a receptor common to both IFN-tau and IFN-alpha in bovine tissues and no indication for a unique IFN-tau-binding polypeptide in endometrium.

Animals↗

PubMed1994

Selective cloning of cDNA for secretory proteins of early embryos. Identification of a transiently expressed kunitz domain protein from preimplantation sheep trophoblast.

The preimplantation ovine conceptus transiently secretes several proteins, including a type I interferon (IFN-tau), that are likely involved in establishment of pregnancy. A method has been developed to identify proteins produced simultaneously with IFN-tau. An antiserum against total ovine conceptus secretory proteins, from which IFN-tau and proteins common to maternal uterine tract secretions had first been removed, was used to immunoscreen cDNA libraries created from mRNA of days 13 and 15 ovine conceptuses. This approach has allowed several unique cDNA to be identified, including one particularly abundant transcript for a novel member of the Kunitz family of serine protease inhibitors. This cDNA encodes a 265-amino acid protein with a 20-amino acid signal sequence. A 64-amino acid Kunitz domain occupies the carboxyl terminus. It is preceded by two similar repeats of 84 residues that bear no obvious similarity to any sequences present in the protein data banks. The protein present in conceptus secretions (M(r) of approximately 14,000) represents only the carboxyl terminus of the molecule. The mRNA for this putative proteinase inhibitor was confined to trophectoderm and was highly expressed for only a few days (approximately 13-18) of development. A similar transcript was detected during the days 17-21 period in cattle embryos. Despite their high expression, no proteinase-inhibitory activity can so far be ascribed to either the ovine or bovine proteins. The P1 residue, an asparagine, is not represented in any other known Kunitz inhibitors.

Amino Acid Sequence↗

PubMed1994

A novel glycoprotein of the aspartic proteinase gene family expressed in bovine placental trophectoderm.

The pregnancy associated glycoproteins (PAG 1) that appear in the maternal serum of cattle and sheep soon after implantation are apparently inactive members of the aspartic proteinase family. Here we describe the isolation of a highly abundant cDNA (PAG 2 cDNA) that represents a second member of this gene family which is structurally related to bovine PAG 1, ovine PAG 1, and pepsin (58%, 58%, and 51% amino acid sequence identity, respectively). The bovine PAG 2 cDNA was identified in two ways. First, the bovine placental library was screened under relatively nonstringent conditions with an ovine PAG 1 cDNA. The second fortuitous approach employed immunoscreening with an antiserum raised against a partially purified factor that competed with bovine LH for binding to the LH receptor on the CL of the ovary. The full-length cDNA (1258 bp) codes for a polypeptide of 376 amino acids. Bovine PAG 2, unlike bovine PAG 1, has a catalytic center with a consensus sequence of amino acids. Its mRNA is expressed in fetal placenta but not in other fetal organs, and is localized to both the mononucleate and binucleate cells of the trophectoderm, whereas PAG 1 is expressed only in binucleate cells. PAG 2 is synthesized by placental explants as a 70-kDa glycoprotein that is processed to several smaller molecules. Western blot analysis of culture media developed with epitope-selected antibodies to PAG 2 reveals several bands ranging in apparent M(r) from 31,000-70,000, which correspond in size to the polypeptides present in the preparation used for immunization.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1994

Multiple regulatory elements are required to direct trophoblast interferon gene expression in choriocarcinoma cells and trophectoderm.

Interferon-tau (IFN tau) is produced exclusively by the trophectoderm during the peri-implantation stage of pregnancy in ruminant ungulate species. Human choriocarcinoma cells (Jar) stably transfected with 1.8 kilobases of promoter from a bovine IFN tau gene ahead of a human GH (hGH) reporter gene constitutively synthesize hGH, but expression is not increased further by exposure to Newcastle disease virus. This and earlier experiments suggest that the transcriptional cues regulating IFN tau expression are distinct from those operating on other type I IFN genes. Transient transfection experiments reveal that two distinct promoter regions are required for full constitutive expression: one proximal (to position -126), which directs basal expression, and a more distal promoter region (positions -280 to -400), which acts as an enhancer. Nuclear extracts prepared from ovine conceptuses during the period of IFN tau expression interact with the proximal promoter region (positions -34 to -126) to form several complexes of high electrophoretic mobility. Although nucleotide sequence motifs potentially capable of binding the transcription factor IRF-1 are present in this region, IRF-1 does not transactivate the IFN tau gene. The distal part of the promoter contains only one region (-322 to -358) that forms a complex with these conceptus nuclear extracts. Both proximal and distal gel shift patterns become dramatically different when IFN tau gene expression ceases, perhaps reflecting the appearance of transcriptional repressors. Together these experiments support the conclusion that the control of IFN tau gene expression is very different from that of other type I IFN genes and that trophoblast-specific expression depends upon distal as well as proximal promoter regulatory elements.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1994

[Molecules of the family of aspartic proteinases in the placenta of ruminants: hormones or proteins?].

The ruminant placenta contains binucleate trophoblastic cells synthesizing proteins, migrating cross the barrier and fusing with endothelial cells of the endometrium. Recently described were two glycoproteins from the family of aspartic proteases, apparently lacking the enzymatic activity: the pregnancy associated glycoproteins I and II (PAGI and PAGII). The first (PAGI) is largely secreted in maternal blood, this characteristic copes with the lack of proteolytic activity. The second (PAGII) is not completely characterized. However, it binds to lutropin (LH) receptors with high affinity. This binding allows to assume that PAGII is likely the same as the bovine chorionic gonadotropin identified earlier (bCG). A better characterization of these glycoproteins (PAGI and PAGII) and other members of the family (PAGIII...) will answer these questions together with the unexplained invasive process of the placenta.

Animals↗

PubMed1994

A role for cytokines in early pregnancy.

Cytokines are expressed in a variety of cell types of the reproductive system, although in most instances their functions are not understood. There are, however, a few instances where a role in early pregnancy has been established. First, preimplantation conceptuses of ruminant ungulate species, such as cattle, sheep and goat, secrete a unique Type I interferon (IFN-tau). By mechanisms that are still unclear, IFN-tau prevents the destruction of the corpus luteum and hence ensures the continued production of progesterone which is essential for continuation of pregnancy. Most like the IFN-tau prevent lutcolysis by modulating the output of a luteolytic hormone, prostaglandin F2 alpha, from the uterus. Depsite this involvement in pregnancy, the IFN-tau possess similar antiproliferative and antiviral activities to other Type I IFN, 1 lambda e.g. IFN-alpha. There are 4-5 genes for IFN-tau in sheep and cattle whose promotor regions are highly conserved and distinct from those of other Type I IFN. These genens are not virally inducible and are expressed only in the trophectoderm (outer epithelium of the developing placenta) from the time of blastocyst hatching to implantation. Leukemia inhibitory factor (LIF) is a multi-functional cytokine which is expressed by uterine endometrium of pregnant mice around day 4 of pregnancy. Female mice lacking a functional LIF gene are fertile but their blastocysts fail to implant, strongly implicating the cytokine in maternal control of implantation. Colony stimulating factors (CSF) are a family of proteins (GM-CSF, CSF-1, G-CSF, and IL-3) that stimulate the cellular proliferation and induction of terminal differentiation of hemopoietic progenitor cells. CSF-1 is expressed in the uterine endometrium of the mouse and human during early pregnancy and its receptor, fms, is present on trophoblast. The osteopetrotic mouse, which represents a natural "knockout" of the CSF-1 gene, exhibits a low rate of fetal implantation and poor fetal viability. It seems likely that CSF-1 expression by the uterus influences growth and differentiation of the placenta. Although different species may utilize different strategies for ensuring developmental and endocrinological coordination between the embryo and the mother, these three examples illustrate that cytokines are likely to be major participants as autocrine factors that direct the events of early pregnancy and not simply as modulators of the maternal immune system.

Animals↗

PubMed1994

Combination therapy of cyclosporine with methotrexate and gold in rheumatoid arthritis (2 pilot studies).

OBJECTIVE: To evaluate the efficacy and toxicity of cyclosporine A (CyA) in combination with gold and methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: Twenty patients with RA with partial response to oral MTX and 20 patients with partial response to im gold had CyA added to their regimen for 6 months, withdrawn over 2 months and the patients monitored for 4 months. RESULTS: There was a significant improvement in joint count, joint score, joint swelling, grip strength and joint pain in patients taking the combination with no significant increase in adverse reactions. CONCLUSION: CyA in combination with gold or MTX may, over a 6 month period, increase efficacy in patients with refractory RA without significant increase in toxicity.

Adult↗

PubMed1993

Interferon-tau.

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Animals↗

PubMed1993

Uteroferrin and intracellular tartrate-resistant acid phosphatases are the products of the same gene.

Uteroferrin (Uf) is a purple acid phosphatase with a bi-iron center. It is the major secretory product of the porcine uterus under the influence of progesterone and supplies iron to the developing fetuses during pregnancy. Tartrate-resistant acid phosphatases (TRAP) are clearly similar to Uf in many of their properties but are generally located intracellularly in lysosomes. To determine whether Uf and intracellular TRAP are distinct gene products, cDNA for the TRAP from pig spleen were compared with Uf cDNA. Although no full-length cDNA for the former were isolated, a TRAP cDNA of 1.1 kilobases was identical in nucleotide sequence to a Uf cDNA (1.42 kilobases) in the region of overlap, which included the entire 3'-end of the transcript and most of the open reading frame. TRAP purified from porcine spleen also had an NH2-terminal amino acid sequence that corresponded to that of Uf purified from uterine secretions and was also similar in sequence to intracellular TRAP isolated from tissues of other species, including ones from human osteoclastomas and spleen. Finally, Southern hybridization analysis with two probes specific for exons 1 and 2 of the Uf gene strongly suggested the presence of only a single gene for acid phosphatases of this class in the pig. A similar analysis performed on human DNA with an exon-specific probe for human TRAP was also consistent with a single gene. It is concluded that the difference in trafficking between a secreted TRAP, such as Uf, and TRAP located in lysosomes is not the result of distinctive primary sequence of the polypeptides and that the variability within species ascribed to such enzymes is most likely the result of minor posttranslational changes.

Acid Phosphatase↗

PubMed1993

Expression of bovine trophoblast interferons by in vitro-derived blastocysts is correlated with their morphological quality and stage of development.

Bovine embryos, whether produced naturally or by in vitro techniques, exhibit considerable variability in morphological quality and develop at different rates. Our objectives have been to determine whether initial expression of trophoblast interferon (IFN-tau) was a reflection of conceptus stage of development or age and whether there was an effect of embryo quality on the amount of IFN-tau produced. Early blastocysts (N = 187) were selected at the onset of blastocoele formation and cultured individually. Embryo quality (excellent, good, or fair: E, G, or F) and developmental stage (early, expanded and hatched blastocysts: BL, EBL, and HBL, respectively) were used in a 3 x 3 factorial complete randomized block design, each block (n = 4) consisting of batches of embryos produced from oocytes in different collections. Quality and developmental stage of embryos and IFN-tau released into the medium were assessed every 24 h. Production of IFN-tau (units/embryo/24 h) was greater (P < 0.01) among hatched blastocysts (HBL; 0.91 +/- 0.08) than expanded blastocysts (EBL; 0.23 +/- 0.04) and early blastocysts (BL; 0.05 +/- 0.08). Embryos of similar developmental stage but differing by 2 days in age released equal amounts of IFN-tau. Expression of antiviral activity increased (P < 0.05) from 27% to 57% to 100% as development proceeded from BL to EBL and to HBL respectively. More IFN-tau was produced by HBL graded G (1.0 +/- 0.1) or E (1.3 +/- 0.1) than by those of F quality (0.5 +/- 0.1). All blastocysts, whatever their quality and developmental stage, contained IFN-tau mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Detection of mRNA for inhibin alpha- and beta A-subunits in bovine ovarian tissues and the effect of in vivo administration of GNRH.

The aims of these studies were to determine which types of bovine ovarian tissue contain mRNA for inhibin/activin subunits and whether administration of GnRH influences concentration of these mRNAs. In experiment (exp.) one, cows in the luteal phase of the estrous cycle were given prostaglandin F2 alpha (PGF2 alpha) to induce luteal regression and injected after 40 hr with saline (n = 5) or 100 micrograms GnRH (n = 6). Ovaries were removed 6 hr later. In exp. two, unilaterally ovariectomized (OVX) heifers (n = 33) in the luteal phase of their estrous cycle were given PGF2 alpha to induce luteal regression. Twelve heifers were OVX without injection of GnRH at 24 (n = 6) or 40 hr (n = 6) after PGF2 alpha. The remaining heifers (n = 21) were given 100 micrograms GnRH at 40 hr after PGF2 alpha injection and OVX 8 (n = 4), 16 (n = 5), 24 (n = 6) or 48 (n = 6) hr after GnRH injection. Total cellular RNA was isolated from large follicles (exp. one and two), small-medium follicles and stromal tissue (SMS) and corpora lutea (CL; exp. one) tissues and analyzed by dot blot and Northern blot techniques by hybridizing with cDNA probes for human inhibin/activin alpha- and beta A-subunits. Large follicles were classified as steroidogenically active (EA) if follicular fluid (FF) concentration of estradiol-17 beta (E2) was greater than progesterone (P4), or if P4 and E2 concentrations in FF were greater than 100 ng/ml, and estrogen inactive (EI) if FF concentration of E2 and P4 did not satisfy these criteria. In exp. one, mRNA for the alpha-subunit was primarily expressed in EA follicles, and detectable in EI follicles, SMS, and CL while beta A-subunit mRNA was detected only in large EA follicles and a few SMS samples. The mRNA (x +/- SEM fmoles/mg DNA) for both subunits of inhibin/activin was higher (P < .05) in EA follicles from GnRH-treated cows (alpha = 210.2 +/- 38.6; beta A = 376.9 +/- 41.0) than in EA follicles from control cows (alpha = 102.5 +/- 28.6; beta A = 170.8 +/- 57.6). Concentration of mRNA for the alpha-subunit of inhibin in other ovarian tissues was not different (P > .10) between saline and GnRH treatments.(ABSTRACT TRUNCATED AT 400 WORDS)

Activins↗

PubMed1993

Porcine uterine retinol-binding proteins are identical gene products to the serum retinol-binding protein.

Retinol-binding proteins (RBP) are secreted by the porcine uterus under the influence of progesterone and consist of multiple charge forms. Evidence has been previously presented by this laboratory that these uterine RBP are distinct from serum RBP. We have followed the secretion of the uterine RBP during two stages of pseudopregnancy, examined their properties and amino acid sequences, and attempted to clone their cDNA. Analysis of the charge forms present in uterine flushes by anion-exchange chromatography showed that forms 1 (p < 0.01) and 3 (p < 0.05) predominated at Day 13, whereas forms 2 (p < 0.05) and 4 (p < 0.01) were most abundant at Day 45. All four charge forms appeared to form stable complexes with transthyretin (TTR) and were recognized by antiserum to human serum RBP on Western blots. Several cDNA clones isolated from an endometrial cDNA library all appeared to code for a protein identical to classical RBP. Off-blot amino acid sequencing of the first ten residues of two of the more divergent charge forms of uterine RBP indicated complete sequence identity with pig serum RBP. These data suggest that the uterine RBP charge forms may be slightly modified forms of a single protein product corresponding to the classical form of RBP. The change in appearance of the charge forms during pseudopregnancy is probably due to chemical modifications. These modifications do not appear to influence the binding of each charge form to TTR.

Amino Acid Sequence↗

PubMed1993

Overexpression of uteroferrin, a lysosomal acid phosphatase found in porcine uterine secretions, results in its high rate of secretion from transfected fibroblasts.

Lysosomal enzymes can, under certain circumstances, be secreted in large amounts. One example is uteroferrin (Uf), an iron-containing, purple-colored acid phosphatase secreted by the uterus of the pig during pregnancy. Uf is identical to the intracellular tartrate-resistant acid phosphatase of pig spleen, yet is the major protein component of uterine secretions. To investigate possible regulatory mechanisms that might direct Uf along a secretory pathway, we expressed Uf in Chinese hamster ovary (CHO) cells under the control of the SV40 early promoter using an expression construct, pX/Uf. The proportion of Uf secreted into the medium relative to the amount retained intracellularly increased as total Uf expression was increased. At transfection doses of 15 micrograms pX/Uf per 10(6) cells, over 80% of the Uf produced in 48 h was secreted. A parallel situation was observed when human cathepsin D was overexpressed in CHO cells. Thus, high production of Uf, as occurs in the uterus in response to progesterone, may overwhelm the intracellular enzymatic and receptor systems that are normally employed to target acid hydrolases to lysosomes, resulting in secretion. Both Uf and cathepsin D secreted by CHO cells possess N-linked, phosphorylated high-mannose oligosaccharide chains. However, the phosphate groups on the oligosaccharide chains of Uf, unlike those on cathepsin D, cannot be readily removed by alkaline phosphatase treatment. These results suggest that the phosphate groups on Uf are masked at least partially by covering N-acetylglucosamine residues and that two mechanisms may contribute to hypersecretion of Uf in the uterus: 1) very high rates of synthesis and 2) partial masking of the mannose 6-phosphate recognition signal.

Acid Phosphatase↗

PubMed1993

Embryo-uterine interactions in pigs during week 2 of pregnancy.

The second week of pregnancy is a particularly critical period for embryonic survival in pigs. Within that time, conceptus oestrogen synthesis is initiated, spacing and final placement of conceptuses is completed, and the signal for extending the functional lifespan of the corpora lutea is received by the mother. There is also a marked increase in blood flow to the uterus and the uterine endometrium produces and secretes nutrient histotrophe. Conceptus-derived oestrogen has been implicated in many of these events. It is also during this period that the trophoblast elongates dramatically and the inner cell mass starts to differentiate into the embryo proper. Here, we critically review the evidence that oestrogen is the sole factor initiating long-term corpus luteum maintenance in pigs. We also review the functions and general properties of the major secretory proteins in histotrophe and the role of oestrogen in controlling their expression. It is now generally accepted that asynchrony within a litter underlies much of the losses of conceptuses that are otherwise genetically normal, but which are lagging in their development; however, the underlying mechanisms remain unclear. Here we hypothesize that oestrogenic compounds derived from more advanced conceptuses or provided prematurely, either by injection or in the diet, trigger a massive increase in uterine expression and secretion of retinol-binding protein laden with retinol. We propose that less developed, smaller conceptuses are least able to contend with the sudden exposure to this potential teratogen at a time when they are particularly susceptible to imbalance in retinol supply. Hence, even though their growth proceeds for a few days, their developmental potential is irrevocably compromised.

Animals↗

PubMed1992

Expression of interleukin-6 in porcine, ovine, and bovine preimplantation conceptuses.

A porcine interleukin-6 (pIL-6) cDNA has been cloned from pig spleen cDNA library to provide information that would allow us to study IL-6 mRNA expression during pregnancy of several domestic Artiodactyla. The cDNA is 1058 bp long and with a single open reading frame that encodes a 212 amino acid polypeptide with 28-residue signal sequence. It shares 61% and 43% amino acid sequence identity with human and mouse IL-6, respectively. PCR procedures with primers designed from regions of sequence conserved between human and pig have been used to identify IL-6 cDNA in lambda gt11 libraries constructed from day 15-16 (sheep), day 17 (cattle), and day 13-17 (pig) conceptus mRNA. The presence of IL-6 mRNA in elongating preimplantation ovine (days 13-25), porcine (days 13-21), and bovine (days 16-20) conceptuses was also demonstrated by PCR after reverse transcription of total ribonucleic acid with reverse transcriptase and by solution hybridization with a pIL-6 cRNA probe. These observations suggest that IL-6 is a product of these early conceptuses and may be involved in early maternal responses to the presence of an embryo within the uterus.

Amino Acid Sequence↗

PubMed1992

Inhibition of lymphocyte proliferation by bovine trophoblast protein-1 (type I trophoblast interferon) and bovine interferon-alpha I1.

Bovine trophoblast protein-1 (bTP-1) is a Type I interferon secreted by the bovine trophoblast from about Day 15 of pregnancy. It is not known whether bTP-1 has functional properties in common with other interferons. The aim of the present study was to determine whether bTP-1 inhibits proliferation of lymphocytes induced by mitogens, mixed lymphocyte cultures (MLC) and interleukin-2 (IL-2) and, if so, whether this activity is similar to that of a related interferon, bovine interferon-alpha I1 (bIFN-alpha I1). Stimulation of lymphocyte proliferation caused by phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) was inhibited by bTP-1 and bIFN-alpha I1 without any reduction in cell viability. Maximum or near-maximum inhibition (less than 50%) was achieved at concentrations of 0.5-5.0 nM of bTP-1 and bIFN-alpha I1. Cells stimulated with PWM were less inhibited than cells stimulated with PHA and Con A. Both bTP-1 and bIFN-alpha I1 inhibited MLC to a greater degree than lectin-stimulated cells (maximum inhibition was 78% or greater). Also, bTP-1 and bIFN-alpha I1 slightly inhibited incorporation of [3H]thymidine ([3H]TdR) induced by the combination of phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), and calcium ionophore A23187. Finally, bTP-1 and bIFN-alpha I1 had bimodal effects on incorporation of [3H]TdR by IL-2-induced lymphocytes. Incorporation of [3H]TdR was increased at 0.005 nM and 0.05 nM concentrations while higher concentrations caused a slight decrease in [3H]TdR incorporation. Results confirm that bTP-1 inhibits lymphocyte proliferation in a manner similar to that caused by the leukocyte-derived interferon, bIFN-alpha I1. Incomplete inhibition of mitogen-induced proliferation and differences in degree of inhibition between various stimulators suggest that bTP-1 and bIFN-alpha I1 preferentially inhibit certain lymphocyte subpopulations. Local inhibition of lymphocyte proliferation caused by bTP-1 may help protect the allogeneic conceptus from immune responses to fetal antigens or regulate the release of cytokines from endometrial lymphocytes.

Animals↗

PubMed1992

Genes for the trophoblast interferons and their distribution among mammals.

The trophoblast interferons (IFN), ovine and bovine trophoblast protein-1 (oTP-1 and bTP-1 respectively), possess many properties in common with other Type I IFN, including antiviral and antiproliferative activities. However, they differ from other IFN subtypes in terms of their specific pattern of expression and poor responsiveness to viral stimulation. We describe here data that suggest that the trophoblast IFN genes are also distinct from other Type I IFN genes with respect to species distribution, promoter organization and transcriptional regulation. These results have important implications in terms of trophoblast IFN gene evolution and add credence to the concept that the trophoblast IFN genes are a distinct IFN gene subtype well suited for their role in early pregnancy.

Animals↗

PubMed1992

Genes for the trophoblast interferons in sheep, goat, and musk ox and distribution of related genes among mammals.

The trophoblast interferons (IFNs) are a family of Type 1 IFN found in domestic ruminants that are most closely related to the little-studied 172-amino-acid IFN-omega. They are produced in massive amounts by the preimplantation conceptus at a time coincident with maternal recognition of pregnancy, and are implicated in playing an important role in this process. Here we report the characterization of four distinct members of the ovine trophoblast IFN (oTP-1) gene family, and demonstrate that they, along with previously characterized bovine trophoblast (bTP-1) genes, possess distinctive promoter sequences when compared to ovine and bovine IFN-omega genes. Genomic Southern blot analysis of numerous mammalian species (zoo blots) indicate that, whereas the IFN-omega are widely distributed among mammals, genes for the trophoblast IFN appear to be limited to ruminant species within the Artiodactyla order. Further polymerase chain reaction (PCR) analysis of trophoblast IFN genes in these ruminant species has permitted isolation of genes for goat and musk ox trophoblast IFN. These data suggest that the trophoblast IFNs are a distinct family of IFN with a limited distribution among mammals.

Animals↗