Mouse melanocortin-4 receptor gene 5'-flanking region imparts cell specific expression in vitro. Academic Article uri icon

abstract

  • Weight homeostasis is exquisitely sensitive to changes in the abundance of melanocortin-4 receptor (MC4-R). To begin to understand the factors that regulate MC4-R gene expression, we determined there are no introns in the gene, there are multiple starts of transcription, and a cluster of 3' ends. A series of MC4-R-luciferase gene reporter chimerics was developed and transfected into cell lines expressing (UMR106; GT1-7; HEK293) and not expressing (Neuro 2A) endogenous MC4-R mRNA. The longest construct, which includes approximately 3.3 kb 5'-flanking, 425 bp 5'-untranslated (UTR) and 1852 bp 3'-flanking, significantly increased luciferase reporter gene expression 24-, 13-, and 3-fold compared to pGL3-basic when expressed in HEK293, UMR106, and GT1-7 cells, respectively. Deletion analysis of mMC4-R 5'-flanking cDNA identified full mMC4-R promoter activity within 178 bp upstream of the major start of transcription. The mMC4-R gene structure and reporter chimerics provide a fundamental framework for the identification of specific factors regulating MC4-R gene expression.

published proceedings

  • Mol Cell Endocrinol

author list (cited authors)

  • Dumont, L. M., Wu, C. S., Aschkenasi, C. J., Elmquist, J. K., Lowell, B. B., & Mountjoy, K. G.

citation count

  • 17

complete list of authors

  • Dumont, LM||Wu, CS||Aschkenasi, CJ||Elmquist, JK||Lowell, BB||Mountjoy, KG

publication date

  • November 2001