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.A...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,Npy1 r,Npy2r,Npy5 r,Agrp,Mc3 r,Mc4r,Crh and CrMr,were significantly greater in Npy-/- rats,whereas Pome 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.展开更多
基金supported by grants from the National Basic Research Program(No.2013CB945001)the National Science Foundation of China(No.81272273)+1 种基金the State High-Tech Program(No.2012AA022403),PUMC Youth Fundthe National Institutes of Health(Nos.NIAAA P60AA007611,U01AA013522 and R24AA015512)
文摘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,Npy1 r,Npy2r,Npy5 r,Agrp,Mc3 r,Mc4r,Crh and CrMr,were significantly greater in Npy-/- rats,whereas Pome 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.
