TITLE

Identification of trans Protein QTL for Secreted Airway Mucins in Mice and a Causal Role for Bpifb1

AUTHOR(S)
Donoghue, Lauren J.; Livraghi-Butrico, Alessandra; McFadden, Kathryn M.; Thomas, Joseph M.; Gang Chen; Grubb, Barbara R.; O'Neal, Wanda K.; Boucher, Richard C.; Kelada, Samir N. P.
PUB. DATE
October 2017
SOURCE
Genetics;Oct2017, Vol. 207 Issue 2, p801
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Mucus hyper-secretion is a hallmark feature of asthma and other muco-obstructive airway diseases. The mucin proteins MUC5AC and MUC5B are the major glycoprotein components of mucus and have critical roles in airway defense. Despite the biomedical importance of these two proteins, the loci that regulate them in the context of natural genetic variation have not been studied. To identify genes that underlie variation in airway mucin levels, we performed genetic analyses in founder strains and incipient lines of the Collaborative Cross (CC) in a house dust mite mouse model of asthma. CC founder strains exhibited significant differences in MUC5AC and MUC5B, providing evidence of heritability. Analysis of gene and protein expression of Muc5ac and Muc5b in incipient CC lines (n = 154) suggested that post-transcriptional events were important regulators of mucin protein content in the airways. Quantitative trait locus (QTL) mapping identified distinct, trans protein QTL for MUC5AC (chromosome 13) and MUC5B (chromosome 2). These two QTL explained 18 and 20% of phenotypic variance, respectively. Examination of the MUC5B QTL allele effects and subsequent phylogenetic analysis allowed us to narrow the MUC5B QTL and identify Bpifb1 as a candidate gene. Bpifb1 mRNA and protein expression were upregulated in parallel to MUC5B after allergen challenge, and Bpifb1 knockout mice exhibited higher MUC5B expression. Thus, BPIFB1 is a novel regulator of MUC5B.
ACCESSION #
125518351

 

Related Articles

  • Unravelling the role of ADAM 33 in asthma. Mahesh, P. A. // Indian Journal of Medical Research;Mar2013, Vol. 137 Issue 3, p447 

    The author examines the role of the ADAM33 gene in asthma. He describes the role of the gene, a disintegrin and metalloproteinase glycoprotein, in both health and disease. He mentions the importance of the interactions between ADAM33 proteins and environmental factors in the pathogenesis of...

  • Regulation of PMA-induced MUC5AC expression by heparin in human bronchial epithelial cells. Li, Qi; Lei, Rui; Zhou, Xiang; Kolosov, Victor; Perelman, Juliy // Molecular & Cellular Biochemistry;Jan2012, Vol. 360 Issue 1/2, p383 

    Mucus hypersecretion is a major pathophysiologic feature in chronic inflammatory airway diseases. Oxidative stress plays a pivotal role in this process. Recent studies have found that heparin has antioxidant effects which can reduce free radical damage. Here, we hypothesized that heparin has...

  • mucin.  // Taber's Cyclopedic Medical Dictionary (2009);2009, Issue 21, p1501 

    A definition of the term "mucin," which refers to a glycoprotein found in mucus present in saliva, bile, skin, glandular tissues, connective tissues, tendon and cartilage, is presented.

  • mucinogen.  // Taber's Cyclopedic Medical Dictionary (2009);2009, Issue 21, p1501 

    A definition of the term "mucinogen," which refers to a glycoprotein that forms a mucin, is presented.

  • mucoid.  // Taber's Cyclopedic Medical Dictionary (2009);2009, Issue 21, p1501 

    A definition of the term "mucoid," which refers to either glycoprotein similar to mucin or muciform, is presented.

  • Large-scale identification and characterization of genetic variants in asthma candidate genes. Jae-Jung Kim; Hyun-Hee Kim; Joo-Hyun Park; Ha-Jung Ryu; JuYoung Kim; Songmean Moon; Haeok Gu; Hung-Tae Kim; Jong-Young Lee; Bok-Ghee Han; Chan Park; Kuchan Kimm; Choon-Sik Park; Jong-Keuk Lee; Bermseok Oh // Immunogenetics;Oct2005, Vol. 57 Issue 9, p636 

    Asthma is a chronic inflammatory disorder of the airways, and a number of genetic loci are associated with the disease. Candidate gene association studies have been regarded as effective tools to study complex traits. Knowledge of the sequence variation and structure of the candidate genes is...

  • The MUC gene family: Their role in diagnosis and early detection of pancreatic cancer. Ringel, Jörg; Löhr, Matthias // Molecular Cancer;2003, Vol. 2, p9 

    The early diagnosis of pancreatic cancer, as well as distinguishing between chronic pancreatitis and malignant pancreatic disease, remains still a clinical problem. Presently, there is no specific tumor marker for diagnosing pancreatic cancer. Mucin-associated marker like CA 19-9 are the most...

  • MUC8 MUCIN GENE UP-REGULATION IN CHRONIC RHINOSINUSITIS. Lee, Heung-Man; Kim, Dae-Hoon; Lee, Sang Hag; Kim, Jung Min; Hwang, Soon Jae // Annals of Otology, Rhinology & Laryngology;Aug2004, Vol. 113 Issue 8, p662 

    The primary mechanisms leading to mucus hypersecretion in chronic sinus inflammation are not well understood. This study aims to investigate the expression of MUC8 messenger RNA (mRNA) and protein and to compare between normal and chronically inflamed sinus mucosae in terms of the expression of...

  • Mucins in the Diagnosis and Therapy of Pancreatic Cancer. Ho, Jenny J.L. // Current Pharmaceutical Design;Dec2000, Vol. 6 Issue 18, p1881 

    Mucins are large glycoproteins that form a protective layer along the lumens of the organs of the gastrointestinal and reproductive tracts. Frequently in tumors of the pancreas there are changes in the structure of mucin carbohydrates and/or levels of apomucin types. Originally mucins were of...

  • Corneal Protection by the Ocular Mucin Secretagogue 15(S)-HETE in a Rabbit Model of Desiccation-induced Corneal Defect. Gamache, Daniel A.; Wei, Zhong-You; Weimer, Lori K.; Miller, Steven T.; Spellman, Joan M.; Yanni, John M. // Journal of Ocular Pharmacology & Therapeutics;Aug2002, Vol. 18 Issue 4, p349 

    The mucin secretagogue 15(S)-HETE was found to stimulate glycoprotein secretion in human ocular tissue at submicromolar concentrations in the present studies. Therefore, the ability of topically applied 15(S)-HETE to preserve corneal integrity was investigated in a rabbit model of...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics