The Carcinoembryonic Antigen Gene Family

The molecular cloning of carcinoembryonic antigen (CEA) and several cross-reacting antigens reveals a basic domain structure for the whole family, which shows structural similarities to the immunoglobulin superfamily. The CEA family consists of approximately 10 genes which are localized in two clusters on chromosome 19. So far, mRNA species for five of these genes have been identified which show tissue variability in their transcriptional activity. Expression of some of these genes in heterologous systems has been achieved, allowing the localization of some epitopes. The characterization of a CEA gene family in the rat and a comparison with its human counterpart has been utilized in the development of an evolutionary model

Intra- and Interspecies Analyses of the Carcinoembryonic Antigen (CEA) Gene Family Reveal Independent Evolution in Primates and Rodents

Various rodent and primate DNAs exhibit a stronger intra- than interspecies cross-hybridization with probes derived from the N-terminal domain exons of human and rat carcinoembryonic antigen (CEA)-like genes. Southern analyses also reveal that the human and rat CEA gene families are of similar complexity. We counted at least 10 different genes per human haploid genome. In the rat, approximately seven to nine different N-terminal domain exons that presumably represent different genes appear to be present. We were able to assign the corresponding genomic restriction endonuclease fragments to already isolated CEA gene family members of both human and rat. Highly similar subgroups, as found within the human CEA gene family, seem to be absent from the rat genome. Hybridization with an intron probe from the human nonspecific cross-reacting antigen (NCA) gene and analysis of DNA sequence data indicate the conservation of noncoding regions among CEA-like genes within primates, implicating that whole gene units may have been duplicated. With the help of a computer program and by calculating the rate of synonymous substitutions, evolutionary trees have been derived. From this, we propose that an independent parallel evolution, leading to different CEA gene families, must have taken place in, at least, the primate and rodent orders

Ubiquitous Nuclear Factors Bind Specifically to a 5′-Region Conserved in Carcinoembryonic Antigen-Related Genes

We recently cloned members of the murine carcinoembryonic antigen (CEA) gene family, some of which are differentially expressed during placental development. By intra- and interspecies sequence comparisons, we identified an element in the putative promoter and/or 5′-nontranslated region which is conserved within all human and rodent CEA-related genes analyzed so far. Using gel retardation analysis and DNasel hypersensitive site mapping, we now show that ubiquitously expressed nuclear factors specifically bind to the conserved region derived from the mouse gene Cea-2 in vitro and probably also in vivo. Another DNasel hypersensitive site lies within or close to a simple sequence motif [(GGA)n] located in the first intron of Cea-2. Such sequences have been reported to play a role in the regulation of certain genes. Therefore, this analysis has identified putative regulatory regions for Cea-2 and possibly CEA-related genes in general

cDNA Cloning Demonstrates the Expression of Pregnancy-Specific Glycoprotein Genes, a Subgroup of the Carcinoembryonic Antigen Gene Family, in Fetal Liver

The pregnancy-specific glycoprotein (PSG) genes constitute a subgroup of the carcinoembryonic antigen (CEA) gene family. Here we report the cloning of four cDNAs coding for different members of the PSG family from a human fetal liver cDNA library. They are derived from three closely related genes (PSG1, PSG4 and PSG6). Two of the cDNA clones represent splice variants of PSG1 (PSG1a, PSG1d) differing in their C-terminal domain and 3′-untranslated regions. All encoded proteins show the same domain arrangement (N-RA1-RA2-RB2-C). Transcripts of the genes PSG1 and PSG4 could be detected in placenta by hybridization with gene-specific oligonucleotides. Expression of cDNA in a mouse and monkey cell line shows that the glycosylated PSG1a protein has a Mr of 65–66 kD and is released from the transfected cells. Sequence comparisons in the C-terminal domain and the 3′-untranslated regions of CEA/PSG-like genes suggests a complex splicing pattern to exist for various gene family members and a common evolutionary origin of these region

cDNA and Gene Analyses Imply a Novel Structure for a Rat Carcinoembryonic Antigen-related Protein

The gene encoding the human tumor marker carcinoembryonic antigen (CEA) belongs to a gene family which can be subdivided into the CEA and the pregnancy-specific glycoprotein subgroups. The corresponding proteins are members of the immunoglobulin superfamily, characterized through the presence of one IgV-like domain and a varying number of IgC-like domains. Since the function of the CEA family is not well understood, we decided to establish an animal model in the rat to study its tissue- specific and developmental stage-dependent expression. To this end, we have screened an 18-day rat placenta cDNA library with a recently isolated fragment of a rat CEA-related gene. Two overlapping clones containing the complete coding region for a putative 709 amino acid protein (rnCGM1; Mr = 78,310) have been characterized. In contrast to all members of the human CEA family, this rat CEA-related protein consists of five IgV-like domains and only one IgC-like domain. This novel structure, which has been confirmed at the genomic level might have important functional implications. Due to the rapid evolutionary divergence of the rat and human CEA gene families it is not possible to assign rnCGM1 to its human counterpart. However, the predominant expression of the rnCGM1 gene in the placenta suggests that it could be analogous to one of the human pregnancy-specific glycoprotein genes

Spatiotemporal Expression of Pregnancy-Specific Glycoprotein Gene rnCGMl in Rat Placenta

As a basis towards a better understanding of the role of the pregnancy-specific glycoprotein (PSG) family in the maintenance of pregnancy, detailed investigations are described on the expression of a recently identified rat PSG gene (rnCGM1) at the mRNA and protein levels. Using specific oligonucleotide primers, rnCGM1 transcripts were identified after reverse transcription, polymerase chain reaction, and hybridization with a radiolabelled, internal oligonucleotide. Transcripts were only found in significant amounts in placenta. In situ hybridization visualized rnCGM1 transcripts at day 14 post coitum (p.c.), in secondary trophoblast giant cells and in the spongiotrophoblast. Only those secondary giant cells lining the maternal decidua were positive. In contrast, primary giant cells did not contain rnCGM1 mRNA. At day 18 p.c., rnCGM1. transcripts were almost exclusively detectable in the spongiotrophoblast. No rnCGM1 transcripts were found in rat embryos of these two developmental stages. Rabbit antisera were generated against the amino-terminal immunoglobulin variable-like domain and against a synthetic peptide containing the last 13 carboxy-terminal amino acids of rnCGM1. Bothe antisera recognized a 124 kDa protein in day 18 rat placental extracts as identified by Western blot analysis. The anti-peptide antiserum recognized a 116 kDa protein in the serum of a 14 day p.c. pregnant rat that is absent from the sera of non-pregnant females. Taken together, these results confirm exclusive expression of rnCGM1 in the rat trophoblast, but unlike human PSG, negligible or no expression is found in other organs, such as fetal liver or salivary glands, indicating a more specialized function of rnCGM1. Its spatiotemporal expression pattern is conducive with a potential role of PSG in protecting the fetus against the maternal immune system and/or in regulating the invasive growth of trophoblast cells

Using the space-borne NASA scatterometer (NSCAT) to determine the frozen and thawed seasons

We hypothesize that the strong sensitivity of radar backscatter to surface dielectric properties, and hence to the phase (solid or liquid) of any water near the surface should make space-borne radar observations a powerful tool for large-scale spatial monitoring of the freeze/thaw state of the land surface, and thus ecosystem growing season length. We analyzed the NASA scatterometer (NSCAT) backscatter from September 1996 to June 1997, along with temperature and snow depth observations and ecosystem modeling, for three BOREAS sites in central Canada. Because of its short wavelength (2.14 cm), NSCAT was sensitive to canopy and surface water. NSCAT had 25 km spatial resolution and approximately twice-daily temporal coverage at the BOREAS latitude. At the northern site the NSCAT signal showed strong seasonality, with backscatter around −8 dB in winter and −12 dB in early summer and fall. The NSCAT signal for the southern sites had less seasonality. At all three sites there was a strong decrease in backscatter during spring thaw (4–6 dB). At the southern deciduous site, NSCAT backscatter rose from −11 to −9.2 dB during spring leaf-out. All sites showed 1–2 dB backscatter shifts corresponding to changes in landscape water state coincident with brief midwinter thaws, snowfall, and extreme cold (Tmax\u3c−25°C). Freeze/thaw detection algorithms developed for other radar instruments gave reasonable results for the northern site but were not successful at the two southern sites. We developed a change detection algorithm based on first differences of 5-day smoothed NSCAT backscatter measurements. This algorithm had some success in identifying the arrival of freezing conditions in the autumn and the beginning of thaw in the spring. Changes in surface freeze/thaw state generally coincided with the arrival and departure of the seasonal snow cover and with simulated shifts in the directions of net carbon exchange at each of the study sites