title: An abundant placental transcript containing an IAP-LTR is allelic to mouse pregnancy-specific glycoprotein 23 (Psg23): cloning and genetic analysis.
abstract: Several families of endogenous retroviruses (ERVs) are expressed in mammalian placental tissues, and are implicated in aspects of placental development and function. We characterized the structure of abundant ERV-related transcripts in mouse placenta. In addition to the 7 kb full-length type I and 5 kb type I deleted intracisternal A-particle (IAP) transcripts, we identified and cloned an abundant 2 kb transcript encoding a novel member of the pregnancy-specific glycoprotein (Psg) gene family, which contains an IAP long terminal repeat (LTR) in the 3' untranslated region (UTR). The polyadenylation signal for the transcript is provided by the inserted LTR sequence. This sequence is allelic to Psg23 and is therefore denoted as Psg23(LTR). The transcript encodes a protein of 471 amino acids and has a domain organisation similar to previously described Psg proteins. Modelling of the protein N-domain produced a structure in good agreement with an existing crystalline structure for mouse sCEACAM1a. The LTR insertion is widely distributed among inbred mouse strains but is not found in 129/sv, CBA/2, or in wild mice. Cloning of the genomic region downstream of the LTR insertion site from the C57Bl/6J strain indicates that the insertion consists of a solo LTR without additional IAP sequence, and identified the original Psg23 polyadenylation signal sequence downstream of the insertion site. Psg23(LTR) was mapped to proximal chromosome 7 using the European collaborative interspecific mouse backcross (EUCIB) panel, and to yeast artificial chromosome (YAC) E072, which contains other members of the Psg gene family, by polymerase chain reaction (PCR). Northern blot analysis of RNA from adult and fetal mouse tissues and in situ hybridization to mid-gestation mouse embryos indicated that Psg23(LTR) is expressed predominantly in placental spongiotrophoblast. We detected a small, but statistically non-significant, bias in favour of transmission of Psg23(LTR) to the offspring of heterozygous parents. However, a larger study would be required to determine whether this allele is selectively advantageous to the developing embryo.
authors.affiliation: Department of Biochemistry, BioSciences Institute, University College Cork, College Road, Cork, Ireland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Ball
authors.forename: Andrew
authors.initials: A
authors.lastname: McLellan
authors.forename: Ben
authors.initials: B
authors.lastname: Collins
authors.forename: John
authors.initials: J
authors.lastname: Coadwell
authors.forename: Francesca
authors.initials: F
authors.lastname: Stewart
authors.forename: Tom
authors.initials: T
authors.lastname: Moore
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D020869:Gene Expression Profiling; D007426:Genes, Intracisternal A-Particle / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009115:Muridae; D020161:Physical Chromosome Mapping; D010920:Placenta / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000737:chemistry / Q000235:genetics*; D011487:Protein Conformation; D051381:Rats; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D020079:Terminal Repeat Sequences / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D018076:DNA, Complementary; D006023:Glycoproteins; D011257:Pregnancy Proteins; C482784:Psg23 protein, mouse