title: Mouse prostasin gene structure, promoter analysis, and restricted expression in lung and kidney.
abstract: 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.
authors.affiliation: Department of Medicine, University of Virginia, Charlottesville, Virginia 22908-0546, USA. gmv4n@virginia.edu
authors.forename: George M
authors.initials: GM
authors.lastname: Verghese
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Tong
authors.forename: Vikash
authors.initials: V
authors.lastname: Bhagwandin
authors.forename: George H
authors.initials: GH
authors.lastname: Caughey
mesh_terms: D020413:3' Untranslated Regions; D024506:5' Flanking Region; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004847:Epithelial Cells / Q000502:physiology; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000502:physiology*; D007684:Kidney Tubules / Q000166:cytology / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000502:physiology; D051381:Rats; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D000099271:Prostasin
chemical_list: D020413:3' Untranslated Regions; D012697:Serine Endopeptidases; D000099271:Prostasin