Published ahead of print on September 4, 2003, doi:10.1165/rcmb.2003-0251OC Am. J. Respir. Cell Mol. Biol., Volume 30, Number 4, April 2004, 519-529 A more recent version of this article appeared on April 1, 2004
Submitted on July 2, 2003 Mouse Prostasin* Gene Structure, Promoter Analysis, and Restricted Expression in Lung and KidneyGeorge M Verghese1*,1 Department of Medicine, University of Virginia, Charlottesville, VA, USA, 2 Cardiovascular Research Institute, University of California-San Francisco, San Francisco, CA, USA * To whom correspondence should be addressed. 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 localize 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.
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