RGD Reference Report - Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight. - Rat Genome Database

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Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight.

Authors: Qiu, B  Bell, RL  Cao, Y  Zhang, L  Stewart, RB  Graves, T  Lumeng, L  Yong, W  Liang, T 
Citation: Qiu B, etal., J Genet Genomics. 2016 Jul 20;43(7):421-30. doi: 10.1016/j.jgg.2016.04.010. Epub 2016 Apr 29.
RGD ID: 11530013
Pubmed: (View Article at PubMed) PMID:27461754
DOI: Full-text: DOI:10.1016/j.jgg.2016.04.010

Neuropeptide Y (NPY) is widely expressed in the central nervous system and influences many physiological processes. It is located within the rat quantitative trait locus (QTL) for alcohol preference on chromosome 4. Alcohol-nonpreferring (NP) rats consume very little alcohol, but have significantly higher NPY expression in the brain than alcohol-preferring (P) rats. We capitalized on this phenotypic difference by creating an Npy knockout (KO) rat using the inbred NP background to evaluate NPY effects on alcohol consumption. Zinc finger nuclease (ZNF) technology was applied, resulting in a 26-bp deletion in the Npy gene. RT-PCR, Western blotting and immunohistochemistry confirmed the absence of Npy mRNA and protein in KO rats. Alcohol consumption was increased in Npy(+/-) but not Npy(-/-) rats, while Npy(-/-) rats displayed significantly lower body weight when compared to Npy(+/+) rats. In whole brain tissue, expression levels of Npy-related and other alcohol-associated genes, Npy1r, Npy2r, Npy5r, Agrp, Mc3r, Mc4r, Crh and Crh1r, were significantly greater in Npy(-/-) rats, whereas Pomc and Crhr2 expressions were highest in Npy(+/-) rats. These findings suggest that the NPY-system works in close coordination with the melanocortin (MC) and corticotropin-releasing hormone (CRH) systems to modulate alcohol intake and body weight.

Annotation

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Npy  (neuropeptide Y)
Npyem6Sage  (neuropeptide Y; zinc finger nuclease induced mutant 6, Sigma Advanced Genetic Engineering Labs)

Objects referenced in this article
0 NP/Iusm-Npyem6Sage null All species

Additional Information