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HTR4 gene structure and altered expression in the developing lung

Hodge, Emily; Nelson, Carl P.; Miller, Suzanne; Billington, Charlotte K.; Stewart, Ceri E.; Swan, Caroline; Malarstig, Anders; Henry, Amanda P.; Gowland, Catherine; Melén, Erik; Hall, Ian P.; Sayers, Ian

Authors

Emily Hodge

Carl P. Nelson

Suzanne Miller

Charlotte K. Billington

Ceri E. Stewart

Caroline Swan

Anders Malarstig

Amanda P. Henry

Catherine Gowland

Erik Melén

Ian P. Hall

Ian Sayers ian.sayers@nottingham.ac.uk



Abstract

Background: Meta-analyses of genome-wide association studies (GWAS) have identified single nucleotide
polymorphisms (SNPs) spanning the 5-hydroxytryptamine receptor 4 (5-HT4R) gene (HTR4) associated with lung
function. The aims of this study were to i) investigate the expression profile of HTR4 in adult and fetal lung tissue
and cultured airway cells, ii) further define HTR4 gene structure and iii) explore the potential functional implications of key SNPs using a bioinformatic approach.

Methods: Following reverse transcription (RT)-PCR in human brain, 5′ rapid amplification of cDNA ends (5′ RACE) was used to examine the exonic structure of HTR4 at the 5′ end. Quantitative (Q)-PCR was used to quantify HTR4 mRNA expression in total RNA from cultured airway cells and whole lung tissue. Publically available gene microarray data on fetal samples of estimated gestational age 7–22 weeks were mined for HTR4 expression. Immunohistochemistry (IHC; in adult and fetal lung tissue) and a radioligand binding assay (in cultured airway cells) were used to analyze 5HT4R protein expression.

Results: IHC in adult lung, irrespective of the presence of chronic obstructive pulmonary disease (COPD), suggested low
level expression of 5-HT4R protein, which was most prominent in alveolar pneumocytes. There was evidence of differential 5-HT4R protein levels during gestation in fetal lung, which was also evident in gene expression microarray data. HTR4 mRNA expression, assessed by Q-PCR, was

Journal Article Type Article
Publication Date Jul 26, 2013
Journal Respiratory Research
Print ISSN 1465-9921
Electronic ISSN 1465-9921
Publisher Humana Press
Peer Reviewed Peer Reviewed
Volume 14
Issue 77
APA6 Citation Hodge, E., Nelson, C. P., Miller, S., Billington, C. K., Stewart, C. E., Swan, C., …Sayers, I. (2013). HTR4 gene structure and altered expression in the developing lung. Respiratory Research, 14(77), doi:10.1186/1465-9921-14-77
DOI https://doi.org/10.1186/1465-9921-14-77
Publisher URL http://respiratory-research.com/content/14/1/77
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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