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General Information
Name
alcohol, response to, NPY-related
FlyBase ID
FBhh0000704
OMIM
Overview

In human and vertebrate model systems, extensive research supports a role for the neuropeptide NPY in modulating neurobiological responses to alcohol and to other drugs of abuse. NPY is known to interact with four G protein-coupled receptor subtypes: NPY1R, NPY2R, NPY4R, and NPY5R. The orthologous neuropeptide in Drosophila is NPF, which acts via Dmel\NPFR, a member of the Neuropeptide Y receptor family. RNAi-targeting constructs and alleles created by targeted recombination, including an amorphic allele, have been generated for Dmel\NPF. RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\NPFR.

The human Hsap\NPY neuropeptide precursor gene has been introduced into flies in the context of a neuronal marker; it has not been used to characterize the role of NPY in response to alcohol. None of the related human neuropeptide receptors has been introduced into flies.

RNAi-effected reduction in either Dmel\NPF or Dmel\NPFR results in neurophysiology phenotypes (assayed in adult olfactory receptor neurons) and behavioral phenotypes; in the case of NPFR, memory defective phenotypes are reported. RNAi directed against NPFR results in decreased alcohol sensitivity; overexpression of NPF results in the opposite phenotype. In adults, conditional disruption of neurons that normally express NPF or NPFR rapidly confers resistance to ethanol sedation, suggesting that the NPF/NPFR neuronal pathway mediates the acute alcohol response. In experiments characterizing reward responses in flies, it was found that artificial activation of NPF neurons was in itself rewarding; this suggests that the NPF/NPFR system may function as a component of a general reward system.

[updated Jan. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: alcohol use disorder, susceptibility to (fly models overview)
Symptoms and phenotype

Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).

The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)

Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).

Alcoholism is a multifactorial, genetically influenced disorder. [from OMIM:103780; 2017.12.19]

Specific Disease Summary: alcohol, response to, NPY-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

Neuropeptide Y (NPY) encodes a neuropeptide that functions through G protein-coupled receptor(s); it is widely expressed in the central nervous system and influences many physiological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. [Gene Cards, NPY; 2018.01.18]

NPY is currently known to interact with four G protein-coupled receptor subtypes: NPY1R, NPY2R, NPY4R, and NPY5R (Robinson and Thiele, 2017; pubmed:29056151).

External links
Disease synonyms
alcohol, response to, NPF/NPFR-related
alcohol, response to, NPY-related
AUD susceptibility, NPY-related
Search term: alcohol use disorder
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

No orthologs identified by standard algorithms; multiple neuropeptide precursor genes in both species. Literature supports orthology of human NPY and Dmel\NPF.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many; multiple in both species.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many; multiple in both species.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many; multiple in both species.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many; multiple in both species.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (2)
    Gene Groups / Pathways
    Comments on ortholog(s)

    Low-scoring ortholog of multiple neuropeptide receptors in human; the NPY receptor genes, NPY1R, NPY2R, NPY4R and NPY5R, are among the more closely related. Dmel\NPFR shares 25-32% identity and 42-51% similarity with these human NPY receptor genes.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Gene Snapshot
    neuropeptide F (NPF) encodes a 36-residue amidated peptide that signals through its receptor NPFR activating an inhibitory G-protein. Major functions of NPF signaling include the regulation of feeding and courtship behavior, metabolism, alcohol sensitivity, aggression as well as learning and memory. It further plays a role in the regulation of circadian behavior, in particular by modifying evening activity and free-running period. [Date last reviewed: 2019-03-14]
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    No orthologs identified by standard algorithms; literature supports orthology of human NPY and Dmel\NPF. Amino acid alignment against the human neuropeptide precusor for NPY shows 28% identity and 43% similarity; of similar size, align along ~60-65% of their length.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (2 groups)
      RNA-RNA
      Interacting group
      Assay
      References
      luminiscence technology, western blot
      luminiscence technology
      Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
      Models Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Models Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      amorphic allele - molecular evidence
      gene targeting by homologous recombination
      amorphic allele - molecular evidence
      gene targeting by homologous recombination
      amorphic allele - molecular evidence
      CRISPR/Cas9
      loss of function allele
      CRISPR/Cas9
      References (16)