Organisation of the mouse and human 5T4 oncofoetal leucine-rich glycoprotein genes and expression in foetal and adult murine tissues.

Abstract

The human 5T4 oncotrophoblast leucine-rich glycoprotein may contribute to the process of placentation or metastasis by modulating cell adhesion, shape and motility. To understand better the role of 5T4 in development and cancer, the gene structure has been elucidated from both human and mouse genomic clones and mRNA expression has been studied in foetal and adult mouse tissues. The protein coding region is located within the second of two exons, the first exon comprising solely of 5'-untranslated region. Upstream there are no TATA or CAAT boxes, but there are a number of potential Sp1 binding sites. The murine and human proteins show a homologous domain organisation of the leucine rich repeats (LRR) and associated N- and C-terminal flanking regions, although the hydrophilic sequence which intervenes between the two LRR domains contains six additional amino acids in the mouse. The signal peptide, transmembrane region and cytoplasmic tail sequences are identical as are 6 out of the 7 potential N-linked glycosylation sites. Mouse 5T4 transcripts are abundant in placenta and also highly expressed in embryos while in adult tissues transcripts are restricted to brain and ovary. These patterns of expression and the genomic organisation are discussed in relation to possible function and other recently described LRR containing proteins.