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首页> 外文期刊>Alcohol >Quantitative trait locus for body weight identified on rat chromosome 4 in inbred alcohol-preferring and -nonpreferring rats: Potential implications for neuropeptide Y and corticotrophin releasing hormone 2
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Quantitative trait locus for body weight identified on rat chromosome 4 in inbred alcohol-preferring and -nonpreferring rats: Potential implications for neuropeptide Y and corticotrophin releasing hormone 2

机译:近亲偏爱和不偏爱近亲大鼠的第4号染色体上体重的定量特征位点:对神经肽Y和促肾上腺皮质激素释放激素2的潜在影响

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摘要

The alcohol-preferring (P) and -nonpreferring (NP) rat lines were developed using bidirectional selective breeding for alcohol consumption (g/kg/day) and alcohol preference (water:ethanol ratio). During a preliminary study, we detected a difference in body weight between inbred P (iP) and inbred NP (iNP) rats that appeared to be associated with the transfer of the Chromosome 4 quantitative trait locus (QTL) seen in the P.NP and NP.P congenic strains. After the initial confirmation that iP rats displayed lower body weight when compared to iNP rats (data not shown), body weight and growth rates of each chromosome 4 reciprocal congenic rat strain (P.NP and NP.P) were measured, and their body weight was consistent with their respective donor strain phenotype, confirming that a quantitative trait locus for body weight mapped to the chromosome 4 interval. Utilizing the newly developed interval-specific congenic strains (ISCS-A and ISCS-B), the QTL interval was further narrowed identifying the following candidate genes of interest: neuropeptide Y (Npy), juxtaposed with another zinc finger gene 1 (Jazf1), corticotrophin releasing factor receptor 2 (Crfr2) and LanC lantibiotic synthetase component C-like 2 (Lancl2). These findings indicate that a biologically active variant(s) regulates body weight on rat chromosome 4 in iP and iNP rats. This QTL for body weight was successfully captured in the P.NP and NP.P congenic strains, and interval-specific congenic strains (ISCSs) were subsequently employed to fine-map the QTL interval identifying the following candidate genes of interest: Npy, Jazf1, Crfr2 and Lancl2. Both Npy and Crfr2 have been previously identified as candidate genes of interest underlying the chromosome 4 QTL for alcohol consumption in iP and iNP rats.
机译:使用双向选择性育种开发了酒精偏爱(P)和非酒精偏爱(NP)大鼠品系,以研究酒精消耗量(g / kg /天)和酒精偏爱(水:乙醇比)。在一项初步研究中,我们发现了自交P(iP)和自交NP(iNP)大鼠之间的体重差异,这似乎与P.NP和NP.P同系菌株。初步确认iP大鼠的体重比iNP大鼠低(数据未显示),然后测量每只4号染色体同系同系大鼠品系(P.NP和NP.P)的体重和生长速率,体重与它们各自的供体菌株表型一致,证实了体重的定量性状基因座被映射到4号染色体区间。利用新开发的区间特异性同系菌株(ISCS-A和ISCS-B),QTL区间进一步缩小,从而确定了以下感兴趣的候选基因:神经肽Y(Npy),与另一个锌指基因1(Jazf1)并置,促肾上腺皮质激素释放因子受体2(Crfr2)和LanC羊毛硫抗生素合成酶成分C-like 2(Lancl2)。这些发现表明,生物学活性变体调节iP和iNP大鼠中大鼠染色体4上的体重。此体重的QTL已成功捕获到P.NP和NP.P同系菌株中,随后采用区间特异性同系菌株(ISCS)精细定位QTL区间,从而确定了以下感兴趣的候选基因:Npy,Jazf1 ,Crfr2和Lancl2。 Npy和Crfr2先前都已被确定为iP和iNP大鼠饮酒的4号染色体QTL的重要候选基因。

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