Asset Details
MbrlCatalogueTitleDetail
Do you wish to reserve the book?
Genetic, epigenetic and pharmacological influences modulating tissue specific regulation of the cannabinoid receptor -1 (CB1) gene; implications for cannabinoid pharmacogenetics
by
Mcewan, Andrew R
, Mackenzie, Alasdair
, Wilson, Dana
, Barrett, Perry
, Pertwee, Roger G
, Hay, Elizabeth A
, Cowie, Philip D
, Ross, Ruth
in
Activator protein 1
/ Alleles
/ Cannabinoid CB1 receptors
/ Clinical trials
/ Clonal deletion
/ Conserved sequence
/ CRISPR
/ DNA methylation
/ Epigenetics
/ Ethanol
/ Genomes
/ Hippocampus
/ Hypothermia
/ Linkage disequilibrium
/ Neuroprotection
/ Nucleotide sequence
/ Pharmacogenetics
/ Regulatory sequences
/ Single-nucleotide polymorphism
/ Transcription factors
/ Transgenic mice
2019
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
You are currently in the queue to collect this book. You will be notified once it is your turn to collect the book.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Genetic, epigenetic and pharmacological influences modulating tissue specific regulation of the cannabinoid receptor -1 (CB1) gene; implications for cannabinoid pharmacogenetics
by
Mcewan, Andrew R
, Mackenzie, Alasdair
, Wilson, Dana
, Barrett, Perry
, Pertwee, Roger G
, Hay, Elizabeth A
, Cowie, Philip D
, Ross, Ruth
in
Activator protein 1
/ Alleles
/ Cannabinoid CB1 receptors
/ Clinical trials
/ Clonal deletion
/ Conserved sequence
/ CRISPR
/ DNA methylation
/ Epigenetics
/ Ethanol
/ Genomes
/ Hippocampus
/ Hypothermia
/ Linkage disequilibrium
/ Neuroprotection
/ Nucleotide sequence
/ Pharmacogenetics
/ Regulatory sequences
/ Single-nucleotide polymorphism
/ Transcription factors
/ Transgenic mice
2019
Oops! Something went wrong.
While trying to remove the title from your shelf something went wrong :( Kindly try again later!
Do you wish to request the book?
Genetic, epigenetic and pharmacological influences modulating tissue specific regulation of the cannabinoid receptor -1 (CB1) gene; implications for cannabinoid pharmacogenetics
by
Mcewan, Andrew R
, Mackenzie, Alasdair
, Wilson, Dana
, Barrett, Perry
, Pertwee, Roger G
, Hay, Elizabeth A
, Cowie, Philip D
, Ross, Ruth
in
Activator protein 1
/ Alleles
/ Cannabinoid CB1 receptors
/ Clinical trials
/ Clonal deletion
/ Conserved sequence
/ CRISPR
/ DNA methylation
/ Epigenetics
/ Ethanol
/ Genomes
/ Hippocampus
/ Hypothermia
/ Linkage disequilibrium
/ Neuroprotection
/ Nucleotide sequence
/ Pharmacogenetics
/ Regulatory sequences
/ Single-nucleotide polymorphism
/ Transcription factors
/ Transgenic mice
2019
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Genetic, epigenetic and pharmacological influences modulating tissue specific regulation of the cannabinoid receptor -1 (CB1) gene; implications for cannabinoid pharmacogenetics
Paper
Genetic, epigenetic and pharmacological influences modulating tissue specific regulation of the cannabinoid receptor -1 (CB1) gene; implications for cannabinoid pharmacogenetics
2019
Request now
and choose the collection method
Overview
Cannabinoid receptor-1 (CB1) represents a potential drug target against conditions that include obesity and substance abuse. However, drug trials targeting CB1 (encoded by the CNR1 gene) have been compromised by differences in patient response. Towards addressing the hypothesis that genetic and epigenetic changes within the regulatory regions controlling CNR1 expression contribute to these differences, we isolated the human CNR1 promotor (CNR1prom) and demonstrate its activity in primary cells and transgenic mice. We also provide evidence of CNR1prom in CB1 autoregulation and its repression by DNA-methylation. We further characterised a conserved regulatory sequence (ECR1) in CNR1 intron 2 that contained a polymorphism in linkage disequilibrium with disease associated SNPs. Deletion of ECR1 from mice using CRISPR genome editing significantly reduced CNR1 expression in the hippocampus. These mice also displayed reduced ethanol intake and hypothermia response to CB1 agonism. Moreover, human specific C-allele variants of ECR1 (ECR1(C)) drove higher levels of CNR1prom activity in hippocampal cells than did the ancestral T-allele. We further demonstrate a role for the AP-1 transcription factor in driving higher ECR1(C) activity. In the context of the known roles of CB1 the current study suggests a mechanism through which ECR1(C) may be neuroprotective in the hippocampus against stress. The cell-specific approaches used in our study to determine the functional effects of genetic and epigenetic changes on the activity of tissue-specific regulatory elements at the CNR1 locus represent an important step in gaining a mechanistic understanding of cannabinoid pharmacogenetics.
Publisher
Cold Spring Harbor Laboratory Press
Subject
This website uses cookies to ensure you get the best experience on our website.