Department of Medical Genetics, University of Alberta, Edmonton, Canada.
Am J Med Genet B Neuropsychiatr Genet. 2009 Dec 5;150B(8):1085-99. doi: 10.1002/ajmg.b.30934.
Magel2 belongs to the MAGE/necdin family of proteins, which have roles in cell cycle, differentiation, and apoptosis. The Magel2 gene is expressed in various brain regions, most notably the hypothalamus. Mice with a targeted deletion of Magel2 display hypoactivity, blunted circadian rhythm, decreased fertility, and increased adiposity. The human ortholog, MAGEL2, is one of a set of paternally expressed, imprinted genes inactivated in most cases of Prader-Willi syndrome, a complex neurodevelopmental disorder. To explore the role of Magel2, brain morphology, brain neurochemistry, and behavior were measured in Magel2-null mice. Brain volume was reduced in specific regions, particularly in the parieto-temporal lobe of the cerebral cortex, the amygdala, the hippocampus, and the nucleus accumbens, as measured by quantitative magnetic resonance imaging. Abnormal neurochemistry was detected in brain samples from adult mice, consisting of decreased serotonin and 5-hydroxyindoleacetic acid in the cortex and the hypothalamus, and decreased dopamine in the hypothalamus. Magel2-null mice displayed relatively normal motor and learning abilities, but exhibited abnormal behavior in novel environments. This study lends support to the important role of the circadian rhythm output gene Magel2 in brain structure and behavior.
Magel2 属于 MAGE/necdin 蛋白家族，该家族在细胞周期、分化和凋亡中发挥作用。Magel2 基因在大脑的多个区域表达，特别是在下丘脑。Magel2 基因敲除的小鼠表现出活动减少、昼夜节律减弱、生育力下降和肥胖增加。人类同源物 MAGEL2 是 Prader-Willi 综合征（一种复杂的神经发育障碍）中大多数情况下失活的一组父源表达、印迹基因之一。为了研究 Magel2 的作用，在 Magel2 基因敲除小鼠中测量了大脑形态、脑神经化学和行为。通过定量磁共振成像测量，发现特定区域的脑体积减少，特别是在大脑皮层的顶颞叶、杏仁核、海马体和伏隔核。在成年小鼠的脑样本中检测到异常的神经化学物质，包括皮质和下丘脑的 5-羟色胺和 5-羟吲哚乙酸减少，以及下丘脑的多巴胺减少。Magel2 基因敲除小鼠表现出相对正常的运动和学习能力，但在新环境中表现出异常行为。这项研究支持昼夜节律输出基因 Magel2 在大脑结构和行为中的重要作用。
