title: Expression and genetic loss of function analysis of the HAT/DESC cluster proteases TMPRSS11A and HAT.
abstract: Genome mining at the turn of the millennium uncovered a new family of type II transmembrane serine proteases (TTSPs) that comprises 17 members in humans and 19 in mice. TTSPs phylogenetically belong to one of four subfamilies: matriptase, hepsin/TMPRSS, corin and HAT/DESC. Whereas a wealth of information now has been gathered as to the physiological functions of members of the hepsin/TMPRSS, matriptase, and corin subfamilies of TTSPs, comparatively little is known about the functions of the HAT/DESC subfamily of proteases. Here we perform a combined expression and functional analysis of this TTSP subfamily. We show that the five human and seven murine HAT/DESC proteases are coordinately expressed, suggesting a level of functional redundancy. We also perform a comprehensive phenotypic analysis of mice deficient in two of the most widely expressed HAT/DESC proteases, TMPRSS11A and HAT, and show that the two proteases are dispensable for development, health, and long-term survival in the absence of external challenges or additional genetic deficits. Our comprehensive expression analysis and generation of TMPRSS11A- and HAT-deficient mutant mouse strains provide a valuable resource for the scientific community for further exploration of the HAT/DESC subfamily proteases in physiological and pathological processes.
authors.affiliation: Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Katiuchia Uzzun
authors.initials: KU
authors.lastname: Sales
authors.forename: John P
authors.initials: JP
authors.lastname: Hobson
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wagenaar-Miller
authors.forename: Roman
authors.initials: R
authors.lastname: Szabo
authors.forename: Amber L
authors.initials: AL
authors.lastname: Rasmussen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bey
authors.forename: Maham F
authors.initials: MF
authors.lastname: Shah
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Molinolo
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Bugge
mesh_terms: D000375:Aging / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D048788:Growth and Development / Q000235:genetics; D006262:Health; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D057057:Serine Proteases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D057057:Serine Proteases; C568601:TMPRSS11A protein, mouse; D012697:Serine Endopeptidases; C112256:human airway trypsin-like protease