In order to identify potential therapeutic targets and markers of disease progression in primary pulmonary hypertension, differential gene expression between primary pulmonary hypertensive and control lung peripheral tissue was examined by suppression subtractive hybridisation. A novel clone was identified in a subtracted primary pulmonary hypertensive cDNA library which had sequence identity to a chromosome 9 clone (AC006241) located in the teleomeric region at 9q34.2–3. The gene spans 86.4 kb and contains 18 exons. Exon prediction programs were used to generate a tentative transcript sequence and PCR primers designed to the 5′- and 3′ ends were used to amplify a full-length cDNA from a lung library. The 2690 bp cDNA (GenBank AF376725) encodes a 552 residue ORF with a theoretical mass of 62 kDa and an isoelectric point 6.72. The protein is predicted to have 7 transmembrane domains and has been named LUng Seven Transmembrane Receptor-1 (LUSTR1) since it is the first of 4 related genes which are widely dispersed in the genome. The genes 2–4 are located on 19p13.3 (18 exons), 15q14–15 (20 exons) and chromosome 2 (not yet defined), respectively. We also have cloned the mouse LUSTR2 cDNA of 1836 bp (GenBank AF376726) (18 exons) which encodes a 562 residue ORF with a theoretical mass of 63.3 kDa and an isoelectric point 7.26. They have 49% identity and 78% similarity. The NT of the proteins have predicted hydrophobic signal peptide sequences and long extracellular domains which are not as highly conserved as the CT 7 transmembrane domains which contain a putative G protein-binding domain in the 3rd intracellular loop with a signature of N-[LIT]-[AV]-[KR]-[LF]-[KS]-L-[FY]-R-H-[FY]. We aim to examine the expression of this gene in primary pulmonary hypertensive and normal lung by in situ hybridisation.
This work was supported by GlaxoWellcome and the Julia Polak Lung Transplant Fund.