Neuroscience 2003 Abstract
| Presentation Number: | 647.12 |
|---|---|
| Abstract Title: | Human cannabinoid receptor 1(CB1) gene structure, polymorphisms, and associations with substance abuse. |
| Authors: |
Zhang, P.*1
; Ishiguro, H.1
; Onaivi, E. S.2
; Lin, z.1
; Uhl, G.1
1Mol. Neurobiol Br., Nat'l Inst. Drug Abuse, NIH, Baltimore, MD 2NJ, 5500 Nathan Shock Drive, 21224, |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Developmental Disorders -- Genetic |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- G-Protein linked Receptors<br />-- Other |
| Session: |
647. Autism & Other Behavioral Disorders Poster |
| Presentation Time: | Tuesday, November 11, 2003 11:00 AM-12:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # WW33 |
| Keywords: | Addiction, Marker, CNR1 |
The G-protein coupled CB1 receptor is the major brain site at which cannabinoid marijuana constituents are psychoactive and the principal brain receptor for endogenous anandamide ligands. CB1 receptor knockout mice display differences in reward exerted by a number of drugs and in ethanol withdrawal syndromes. Initial association studies within CB1 coding exon and 3’flanking region variants suggested possible roles for human CB1 variants in vulnerabilities to psychoses or addictions. These sorts of data make elucidation of the complete CB1 receptor gene, its variants, and their haplotypes of importance. Accordingly, we have worked to improve definition of the human CB1 receptor gene and mRNAs. Using Northern and RACE analyses, we identified three novel exons that encode CB1 mRNA 5’ UTR sequences. We identified 5 novel splice variant sequences that incorporate these exons in varying patterns, and quantitated them by RT-PCR. Northern analyses using exon-specific probes reveal one major and three minor mRNA species in brain mRNA. Transcription initiation sites determined by primer extension and RT-PCR fit with these exonic definitions and explain the observed sizes of CB1 mRNA species. Further, sequences 5’ the first exon contain putative promoter/ enhancer elements that can drive luciferase expression in SK-N-SH cell. This more complete gene structural information allows improved definition of common human CB1 polymorphisms and haplotypes in Caucasian and African-American research volunteers.Some of the 5’ markers are present at different frequencies in initial studies of > 200 Caucasian polysubstance abuser and control samples. The CB1 receptor gene is thus richer than previously appreciated, and contains regulatory region haplotypes that may play roles in human addiction vulnerabilities.
Supported by NIDA IRP
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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