Characterizing a novel promoter of mouse MOR-1 gene

Project Details

Description

DESCRIPTION (provided by the applicant): The primary goal of this application
is to obtain a better understanding of transcriptional regulation of the mu
opioid receptor gene (Oprm) through molecular biological means and transgenic
techniques. Soon after the MOR-1 cDNAs were cloned, the promoter (El promoter)
and structure (exons 1-4) of the original MOR-1 gene were identified and
characterized. This was soon followed by the isolation of two splice forms,
MOR-1A and MOR-IB. The diversity of the MOR-l gene was further illustrated by
our recent identification of an additional nine exons, twelve splice variants
and a novel promoter associated with one of the new exons (E11promoter). This
application focuses on elucidating the detailed structure and function of the
E11 promoter and its relationships with E1 promoter. The E11 promoter is
located at about10 kb upstream of the original E1 promoter. Alternative
splicing of the transcripts driven by the E11 promoter yield eight variants
encoding a number of novel proteins as well as the original MOR-1 protein.
Three of the variants regulated by the E11 promoter generate the original MOR-1
protein. Thus, this single protein can be generated by four splice variants of
the mu opioid receptor gene under the control of two distinct promoters.
Differential expression of the variant mRNAs in various brain regions revealed
region-specific RNA processing. Neuronal promoter activities with a core
promoter and a negative element have been suggested. The specific aims to
achieve the overall goal are: (1) Identification of cis-acting elements in E11
promoter region through mutant analysis; (2) Isolation of DNA-binding proteins
that regulate promoter activities; (3) Investigation of the E11 promoter and
its relationships with E1 promoter in transgenic mice. My long-term goal is to
understand the mechanisms by which the MOR-1 gene is regulated and to gain
insights into the pharmacological and physiological significance of its
regulation. The significance of the E11 promoter and its associated variants is
suggested by antisense mapping studies in which two antisense probes targeting
exon 11 blocked spinal morphine and supraspinal M6G analgesia. The knowledge
obtained from the application will help to determine the complexity and
functional importance of MOR-l gene regulation, establish the cell models and
the transgenic animal models for studying its gene regulation, and provide
potential targets for developing novel drugs useful in pain control and drug
abuse.
StatusFinished
Effective start/end date9/27/021/31/14

Funding

  • National Institute on Drug Abuse: $9,855.00
  • National Institute on Drug Abuse: $277,375.00
  • National Institute on Drug Abuse: $316,143.00
  • National Institute on Drug Abuse: $374,000.00
  • National Institute on Drug Abuse: $359,152.00
  • National Institute on Drug Abuse: $359,152.00
  • National Institute on Drug Abuse: $370,260.00
  • National Institute on Drug Abuse: $277,375.00
  • National Institute on Drug Abuse: $276,034.00
  • National Institute on Drug Abuse: $374,000.00
  • National Institute on Drug Abuse: $277,375.00

ASJC

  • Genetics
  • Medicine(all)
  • Molecular Biology
  • Neuroscience(all)
  • Pharmacology

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.