Gammie S C, Auger A P, Jessen H M, Vanzo R J, Awad T A, Stevenson S A
Department of Zoology, and Neuroscience Training Program, University of Wisconsin, Madison, WI 53706, USA.
Genes Brain Behav. 2007 Jul;6(5):432-43. doi: 10.1111/j.1601-183X.2006.00271.x. Epub 2006 Aug 29.
We previously applied selective breeding on outbred mice to increase maternal aggression (maternal defense). In this study, we compared gene expression within a continuous region of the central nervous system (CNS) involved in maternal aggression (hypothalamus and preoptic regions) between lactating selected (S) and nonselected control (C) mice (n= 6 per group). Using microarrays representing over 40,000 genes or expressed sequence tags, two statistical algorithms were used to identify significant differences in gene expression: robust multiarray and the probe logarithmic intensity error method. Approximately 200 genes were identified as significant using an intersection from both techniques. A subset of genes was examined for confirmation by real-time polymerase chain reaction (PCR). Significant decreases were found in S mice for neurotensin and neuropeptide Y receptor Y2 (both confirmed by PCR). Significant increases were found in S mice for neuronal nitric oxide synthase (confirmed by PCR), the K+ channel subunit, Kcna1 (confirmed by PCR), corticotrophin releasing factor binding protein (just above significance using PCR; P= 0.051) and GABA A receptor subunit 1A (not confirmed by PCR, but similar direction). S mice also exhibited significantly higher levels of the neurotransmitter receptor, adenosine A1 receptor and the transcription factors, c-Fos, and Egr-1. Interestingly, for 24 genes related to metabolism, all were significantly elevated in S mice, suggesting altered metabolism in these mice. Together, this study provides a list of candidate genes (some previously implicated in maternal aggression and some novel) that may play an important role in the production of this behavior.
我们之前对远交群小鼠进行了选择性育种，以增强母性攻击行为（母性防御）。在本研究中，我们比较了泌乳期选择品系（S）和未选择的对照品系（C）小鼠（每组n = 6）中，参与母性攻击行为的中枢神经系统（CNS）连续区域（下丘脑和视前区）内的基因表达。使用代表超过40,000个基因或表达序列标签的微阵列，运用两种统计算法来鉴定基因表达的显著差异：稳健多阵列法和探针对数强度误差法。通过两种技术的交集，大约鉴定出200个显著基因。通过实时聚合酶链反应（PCR）对一部分基因进行检测以作确认。在S小鼠中发现神经降压素和神经肽Y受体Y2显著降低（均通过PCR确认）。在S小鼠中发现神经元型一氧化氮合酶（通过PCR确认）、钾离子通道亚基Kcna1（通过PCR确认）、促肾上腺皮质激素释放因子结合蛋白（PCR结果略高于显著性水平；P = 0.051）和GABAA受体亚基1A显著增加（未通过PCR确认，但方向相似）。S小鼠还表现出神经递质受体腺苷A1受体以及转录因子c-Fos和Egr-1的水平显著更高。有趣的是，对于24个与代谢相关的基因，在S小鼠中均显著升高，表明这些小鼠的代谢发生了改变。总之，本研究提供了一份候选基因列表（一些之前与母性攻击行为有关，一些是新发现的），这些基因可能在这种行为的产生中发挥重要作用。
