Treadwell Julie A, Pagniello Kara B, Singh Shiva M
Department of Biology and Division of Medical Genetics, University of Western Ontario, London, Ontario, Canada N6A 5B7.
Behav Genet. 2004 Jul;34(4):425-39. doi: 10.1023/B:BEGE.0000023648.78190.ee.
Genetic strains of mice represent an important resource for research on the biological determinants of complex diseases and behavioral phenotypes. To date, the approaches used have had little success in identifying causal genes. We have evaluated brain gene expression in C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains using differential display to identify a number of sequences showing significant expression differences between the two strains. These differences were confirmed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. Knowing that B6 and D2 mouse strains differ for a number of behavioral phenotypes, we asked whether this difference in brain gene expression could explain any of these traits. Here, we show that the expression of two of these genes, retinaldehyde binding protein 1 (Rlbp1) and syntaxin 12 (Stx12), co-segregate with the ethanol preference phenotype in a B6D2 F2 population. Our results suggest a potential role for Rlbp1 and Stx12 in ethanol preference in mice, a conclusion supported by the location of these genes in quantitative trait loci (QTL) regions for this phenotype. This experimental approach has the potential for a broad application in the assessment of the roles of differentially expressed genes in a variety of complex phenotypes, with the advantage of identifying novel and potentially causal candidate genes directly.
小鼠的遗传品系是研究复杂疾病和行为表型的生物学决定因素的重要资源。迄今为止，所采用的方法在确定因果基因方面收效甚微。我们利用差异显示技术评估了近交系小鼠C57BL/6J（B6）和DBA/2J（D2）的脑基因表达，以鉴定出一些在这两个品系间表现出显著表达差异的序列。这些差异通过半定量逆转录聚合酶链反应（RT-PCR）和实时PCR得到了证实。鉴于B6和D2小鼠品系在多种行为表型上存在差异，我们探究了这种脑基因表达的差异是否能够解释这些性状中的任何一种。在此，我们表明，在B6D2 F2群体中，这两个基因，即视黄醛结合蛋白1（Rlbp1）和 syntaxin 12（Stx12）的表达与乙醇偏好表型共分离。我们的结果表明Rlbp1和Stx12在小鼠乙醇偏好中可能发挥作用，这一结论得到了这些基因在该表型的数量性状位点（QTL）区域中的定位的支持。这种实验方法在评估差异表达基因在各种复杂表型中的作用方面具有广泛应用的潜力，其优点是能够直接鉴定出新的和潜在的因果候选基因。
