Conti Lisa H, Jirout Martin, Breen Laura, Vanella Jessica J, Schork Nicholas J, Printz Morton P
Department of Pharmacology, 0636, University of California, San Diego, La Jolla, California, USA.
Behav Genet. 2004 Jan;34(1):93-103. doi: 10.1023/B:BEGE.0000009479.02183.1f.
Anxiety disorders are phenotypically complex and may involve multiple genetic influences on many neurotransmitter systems. Rodent tests used to investigate genetic influences on anxiety-like phenotypes have face and predictive validity as models for anxiety in humans. If multiple genes contribute additively to a trait, the trait will be continuously distributed and be amenable to detection of associations between allelic variation at specific chromosomal loci and the phenotypes being studied via quantitative trait loci (QTL) mapping. The elevated plus-maze test provides quantitative measures of both anxiety-like and locomotion phenotypes. Using this test, we assessed four phenotypes in a set of 22 rat recombinant inbred (RI) strains derived from Brown Norway (BN.Lx /Cub) and Spontaneously Hypertensive rat (SHR/Ola) progenitors. QTL analyses were used to determine whether allelic variation at specific chromosomal loci contribute significantly to RI strain-dependent variance in each phenotype. Significant QTL for an anxiety phenotype were found on chromosomes 2, 5, 6, and 7. For a phenotype reflecting both anxiety and locomotion, QTL were found on chromosomes 2, 7, and 8, while for a locomotion phenotype, significant QTL were found on chromosomes 3 and 18.
焦虑症在表型上较为复杂，可能涉及多个基因对多种神经递质系统的影响。用于研究基因对焦虑样表型影响的啮齿动物试验作为人类焦虑症模型具有表面效度和预测效度。如果多个基因对某一性状有累加作用，该性状将呈连续分布，并且适合通过数量性状基因座（QTL）定位来检测特定染色体位点的等位基因变异与所研究表型之间的关联。高架十字迷宫试验提供了焦虑样和运动表型的定量测量方法。利用该试验，我们在一组由挪威棕色大鼠（BN.Lx /Cub）和自发性高血压大鼠（SHR/Ola）亲本衍生而来的22个大鼠重组近交（RI）品系中评估了四种表型。QTL分析用于确定特定染色体位点的等位基因变异是否对每个表型中RI品系依赖性变异有显著贡献。在2号、5号、6号和7号染色体上发现了焦虑表型的显著QTL。对于反映焦虑和运动的表型，在2号、7号和8号染色体上发现了QTL，而对于运动表型，在3号和18号染色体上发现了显著的QTL。
