Published ahead of print on September 4, 2003, doi:10.1165/rcmb.2003-0251OC
© 2004 American Thoracic Society DOI: 10.1165/rcmb.2003-0251OC Mouse Prostasin Gene Structure, Promoter Analysis, and Restricted Expression in Lung and KidneyDepartment of Medicine, University of Virginia, Charlottesville, Virginia; and Cardiovascular Research Institute, University of California, San Francisco, California Address correspondence to: George M. Verghese, P.O. Box 800546, University of Virginia, Charlottesville, VA 22908-0546. E-mail: gmv4n{at}virginia.edu Human prostasin is a membrane-anchored serine peptidase hypothesized to regulate lung epithelial sodium transport. It belongs to a unique family of genes on chromosome 16p11.2/13.3. Here we describe genomic cloning, promoter analysis, and expression of prostasin's mouse ortholog. The 4.3-kb mouse prostasin gene (prss8) has a six-exon organization identical to human prostasin. Prss8 spans two signal tagged-sites localized to chromosome 7. Multiple mRNA transcripts arise from two consensus initiator elements of a TATA-less promoter and an alternatively spliced, 5' untranslated region intron. Reporter assay establishes that the initiator elements and a GC-rich domain comprise the core promoter and identifies 5' flanking regions with strong enhancer and repressor activity. The 3' untranslated region overlaps the 3' untranslated region of the Myst1 gene oriented tail-to-tail at this locus. Prss8 is highly transcribed in pancreas, kidney, submaxillary gland, lung, thyroid, prostate, and epididymis, and is developmentally regulated. Using selective riboprobes and antibodies to mouse prostasin, we localized its expression to lung airway epithelial and alveolar type II cells and kidney cortical tubule epithelium. Mouse prostasin highly resembles its human ortholog in gene organization and tissue specificity, including strong expression in pulmonary epithelium, suggesting that mice will be useful for probing prostasin's functions in vivo.
Abbreviations: alveolar type II cell, AT II • Basic Local Alignment Search Tool, BLAST • channel-activating protease 1, CAP1 • distal intestinal serine protease, DISP • epithelial sodium channel, ENaC • eosinophil serine protease, esp-1 • expressed sequence tag, EST • fluorescein isothiocyanate, FITC • glycosylphosphatidylinositol, GPI • male orienting factor, MOF • polymerase chain reaction, PCR • mouse prostasin gene, prss8 • human prostasin gene, PRSS8 • rapid amplification of cDNA ends, RACE • RNA ligase-mediated RACE, RLM-RACE • reverse transcription, RT • sequence tagged sites, STS • Transcriptional Element Search Software, TESS • tyramide signal amplification, TSA • untranslated region, UTR This article has been cited by other articles:
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