An abundant placental transcript containing an IAP-LTR is allelic to mouse pregnancy-specific glycoprotein 23 (Psg23):: cloning and genetic analysis

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 C57B1/6J 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 deter-mine whether this allele is selectively advantageous to the developing embryo. (C) 2003 Elsevier B.V All rights reserved.