Hypothalamus transcriptome profile suggests an anorexia-cachexia syndrome in anx/anx mouse model

The anx/anx mouse displays poor appetite and lean appearance and is considered a good model for the study of anorexia nervosa. To identify new genes involved in feeding behavior and body weight regulation we performed an expression profiling in the hypothalamus of the anx/anx mice. Using commercial microarrays we detected 156 differentially expressed genes and validated 92 of those using TaqMan low-density arrays. Our results showed an enrichment of deregulated genes involved in cell death, cell morphology and cancer as well as an alteration of several signaling circuits involved in energy balance including neuropeptide Y and melanocortin signaling. The expression profile along with the phenotype let us to conclude that anx/anx mice resemble the anorexia-cachexia syndrome typically observed in cancer, infection with human immunodeficiency virus or chronic diseases rather than starvation, and that anx/anx mice could be considered a good model for the treatment and investigation of this condition. Keywords: genetic mutation analysis Total RNA expression profile comparison between 3 pairs of anx/anx mice and wild type littermates in brain hypothalamus and neocortex

anx/anx小鼠表现出食欲减退与体瘦表型，被视作神经性厌食症研究的理想动物模型。为鉴定参与摄食行为与体重调控的新基因，我们对anx/anx小鼠的下丘脑（hypothalamus）开展了表达谱分析。我们采用商业化微阵列（microarrays）筛选得到156个差异表达基因，并通过TaqMan低密度阵列（TaqMan low-density arrays）对其中92个基因进行了验证。研究结果显示，失调基因在细胞死亡、细胞形态调控及癌症相关通路中显著富集；同时，能量平衡相关的多条信号通路发生改变，包括神经肽Y（neuropeptide Y）与黑皮质素信号通路。结合表达谱数据与表型特征，我们得出如下结论：anx/anx小鼠的表型更接近癌症、人类免疫缺陷病毒（human immunodeficiency virus，HIV）感染或慢性疾病中常见的厌食-恶病质综合征，而非单纯饥饿所致；因此anx/anx小鼠可作为该病症的治疗研究与机制探索的理想模型。
关键词：基因突变分析；3对anx/anx小鼠与野生型同窝幼鼠的脑下丘脑及新皮层（neocortex）总RNA表达谱比较