Aksu Soner, Koczan Dirk, Renne Ulla, Thiesen Hans-Jurgen, Brockmann Gudrun A
Institute for Animal Sciences, Humboldt-Universität zu Berlin, Invalidenstrasse 42, 10115 Berlin, Germany.
J Appl Genet. 2007;48(2):133-43. doi: 10.1007/BF03194671.
Recently, quantitative trait loci (QTLs) for body weight and obesity have been mapped in an intercross population between the high body weight-selected mouse line DU6i and the inbred line DBA/2. Most QTLs were highly significant, but had small effects only. Under the hypothesis that small-effect QTLs might result from changes in gene activity, our strategy to identify candidate genes for the observed effects was directed towards the identification of differentially expressed genes. Therefore, here we compare the transcription profile of about 11 000 genes in epididymal fat tissues of males of two high body weight-selected (DU6 and DU6i) and two unselected mouse lines (DUKs and DBA/2). For the hybridisation of GeneChips, we used pooled samples of 20 individual mice. By pair-wise comparisons between selected and unselected mouse lines, a set of 77 genes was identified representing genes whose level of expression differed between obese and lean mouse strains. According to the functional classification of genes, 69 differentially expressed genes were involved in regulatory and metabolic pathways, cell division, cell stability, or immune response, and thus might have an effect on body weight and fat accumulation. 14 out of these genes, occur in QTL regions for body weight or abdominal fat weight. Further analyses are necessary to discriminate between genes directly causing QTL effects and indirectly regulated differentially expressed genes.
最近,在高体重选择品系DU6i和近交系DBA/2之间的杂交群体中,已对体重和肥胖的数量性状基因座(QTL)进行了定位。大多数QTL具有高度显著性,但效应较小。基于小效应QTL可能是由基因活性变化导致的这一假设,我们识别观察到的效应的候选基因的策略是针对识别差异表达基因。因此,我们比较了两个高体重选择品系(DU6和DU6i)以及两个未选择品系(DUKs和DBA/2)雄性小鼠附睾脂肪组织中约11000个基因的转录谱。对于基因芯片杂交,我们使用了20只个体小鼠的混合样本。通过对选择品系和未选择品系进行两两比较,鉴定出一组77个基因,这些基因代表肥胖和瘦小鼠品系之间表达水平不同的基因。根据基因的功能分类,69个差异表达基因参与调控和代谢途径、细胞分裂、细胞稳定性或免疫反应,因此可能对体重和脂肪积累有影响。其中14个基因位于体重或腹部脂肪重量的QTL区域。需要进一步分析以区分直接导致QTL效应的基因和间接调控的差异表达基因。