| First Author | O'Connell TD | Year | 2001 |
| Journal | Mol Pharmacol | Volume | 59 |
| Issue | 5 | Pages | 1225-34 |
| PubMed ID | 11306707 | Mgi Jnum | J:69078 |
| Mgi Id | MGI:1934000 | Doi | 10.1124/mol.59.5.1225 |
| Citation | O'Connell TD, et al. (2001) Cloning and Characterization of the Mouse alpha1C/A-Adrenergic Receptor Gene and Analysis of an alpha1C Promoter in Cardiac Myocytes: Role of an MCAT Element That Binds Transcriptional Enhancer Factor-1 (TEF-1). Mol Pharmacol 59(5):1225-34 |
| abstractText | alpha1-Adrenergic receptor (AR) subtypes in the heart are expressed by myocytes but not by fibroblasts, a feature that distinguishes alpha1-ARs from beta-ARs. Here we studied myocyte-specific expression of alpha1-ARs, focusing on the subtype alpha1C (also called alpha1A), a subtype implicated in cardiac hypertrophic signaling in rat models. We first cloned the mouse alpha1C-AR gene, which consisted of two exons with an 18 kb intron, similar to the alpha1B-AR gene. The receptor coding sequence was >90% homologous to that of rat and human. alpha1C-AR transcription in mouse heart was initiated from a single Inr consensus sequence at -588 from the ATG; this and a putative polyadenylation sequence 8.5 kb 3' could account for the predominant 11 kb alpha1C mRNA in mouse heart. A 5'-nontranscribed fragment of 4.4 kb was active as a promoter in cardiac myocytes but not in fibroblasts. Promoter activity in myocytes required a single muscle CAT (MCAT) element, and this MCAT bound in vitro to recombinant and endogenous transcriptional enhancer factor-1. Thus, alpha1C-AR transcription in cardiac myocytes shares MCAT dependence with other cardiac-specific genes, including the alpha- and beta-myosin heavy chains, skeletal alpha-actin, and brain natriuretic peptide. However, the mouse alpha1C gene was not transcribed in the neonatal heart and was not activated by alpha1-AR and other hypertrophic agonists in rat myocytes, and thus differed from other MCAT-dependent genes and the rat alpha1C gene. |
