MRI and in situ hybridization reveal early disturbances in brain size and gene expression in the megencephalic (mceph/mceph) mouse
MRI and in situ hybridization reveal early disturbances in brain size and gene expression in the megencephalic (mceph/mceph) mouse
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DOI：
10.1111/j.1460-9568.2003.02994.x
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发表时间：
2003-12-01
影响因子：
3.4
通讯作者：
Spenger, C
中科院分区：
文献类型：
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作者：
Diez, M;Schweinhardt, P;Spenger, C
巨脑畸形的小鼠模型mceph/mceph携带与振动器相关的电压门控钾通道基因1的截断缺失。受影响的小鼠表现出神经障碍和运动功能障碍。症状开始出现在3-4周大的时候。大脑增大的原因尚不清楚。为了阐明疾病发展的早期事件，我们使用磁共振成像(MRI)来量化同一小鼠在3、8和12周时几个离散大脑区域的大小随时间的增加。我们还分析了神经肽和生长因子的标记物，以探索它们在早期阶段的可能参与。结果显示，在3周大的时候，大脑的总冠状面积就已经扩大了。8周及以后，大脑总体积、腹侧皮质、海马结构和大脑皮质均增大。丘脑、脑干、小脑和脊髓即使在12周时也与对照组无差异。我们还报告了脑源性神经营养因子、胰岛素样生长因子结合蛋白6和几种神经肽在2周和3周龄时的表达明显紊乱，即在观察到明显的行为表型之前。这些结果客观地描述了mceph/mceph小鼠不同脑区的大小变化，并表明某些分子可能参与了这些变化的早期过程。
The mouse model for megencephaly, mceph/mceph, carries a truncating deletion in the Shaker-related voltage gated potassium channel gene 1. Affected mice display neurological disturbances and motor dysfunctions. Symptoms begin to show at 3-4 weeks of age. The cause of the brain enlargement is not clear. To elucidate early events in the development of the disease we used magnetic resonance imaging (MRI) to quantify, over time, the increase in size of several discrete brain regions in the same mice at 3, 8 and 12 weeks of age. We also analysed markers for neuropeptides and growth factors to explore their possible involvement at an early stage. The results show an enlargement of the total coronal area of the brain already at 3 weeks of age. Total brain volume, ventral cortex, hippocampal formation and cerebral cortex were enlarged at 8 weeks and onwards. Thalamus, brainstem, cerebellum and spinal cord did not differ from controls even at 12 weeks. We also report distinct disturbances in the expression of brain-derived neurotrophic factor, insulin-like growth factor binding protein 6 and several neuropeptides at 2 and 3 weeks of age, that is, before an obvious behavioural phenotype can be observed. These results provide an objective description of the size changes in different brain regions of the mceph/mceph mouse, and suggest that certain molecules could be involved in the early processes underlying these changes.