التفاصيل البيبلوغرافية
| العنوان: |
HTR4 gene structure and altered expression in the developing lung |
| المؤلفون: |
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 |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2013 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
5-hydroxytryptamine, HTR4, 5-HT4R, Splice variant, Lung development, COPD, GPCR |
| الوصف: |
Background Meta-analyses of genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) spanning the 5-hydroxytryptamine receptor 4 (5-HT 4 R) 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 5HT 4 R protein expression. Results IHC in adult lung, irrespective of the presence of chronic obstructive pulmonary disease (COPD), suggested low level expression of 5-HT 4 R protein, which was most prominent in alveolar pneumocytes. There was evidence of differential 5-HT 4 R protein levels during gestation in fetal lung, which was also evident in gene expression microarray data. HTR4 mRNA expression, assessed by Q-PCR, was <0.5% relative to brain in total adult lung tissue and in human airway smooth muscle (HASM) and bronchial epithelial cells (HBEC) derived from adult donors. Radioligand binding experiments also indicated that HBEC and HASM cells did not express a significant 5-HT 4 R population. 5′ RACE in brain identified a novel N -terminal variant, containing an extended N- terminal sequence. The functional significance of key HTR4 SNPs was investigated using the encyclopedia of DNA elements consortium (ENCODE) dataset. These analyses identified ... |
| نوع الوثيقة: |
report |
| اللغة: |
English |
| العلاقة: |
http://respiratory-research.com/content/14/1/77Test |
| الإتاحة: |
http://respiratory-research.com/content/14/1/77Test |
| حقوق: |
Copyright 2013 Hodge et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.4C3C6194 |
| قاعدة البيانات: |
BASE |
