Giladi Eliezer, Hill Joanna M, Dresner Efrat, Stack Conor M, Gozes Illana
Department of Human Molecular Genetics and Biochemistry, Tel-Aviv University, Tel-Aviv, 69978, Israel.
J Mol Neurosci. 2007;33(3):278-83. doi: 10.1007/s12031-007-9003-0. Epub 2007 Oct 2.
Vasoactive intestinal peptide (VIP) is an important mediator of development during the neural tube closure period of embryogenesis and may regulate, in part, the expression of activity-dependent neuroprotective protein (ADNP), which is essential for neural tube closure and embryogenesis. To evaluate the impact of VIP expression in vivo on ADNP and the related protein ADNP2 the current study examined gene expression in adult wild-type (VIP +/+) and VIP null (VIP -/-) offspring of VIP deficient mothers (VIP+/-) comparing them to wild-type offspring of wild-type mothers. Quantitative real time polymerase chain reaction (PCR), using an ABI Prisma cycler revealed regionally specific reductions of ADNP mRNA in the brains of VIP null mice compared with the brains of wild-type offspring of a wild-type mother. ADNP was significantly reduced in the cortex and hypothalamus of VIP null mice, but not in the hippocampus or thalamus. ADNP2 exhibited a similar pattern but reached a statistically significant reduction only in the hypothalamus. The mRNA for ADNP and ADNP2 also tended to be reduced in the cortex and hippocampus of the wild-type littermates of the VIP null mice, indicating that the VIP genotype of the mother may have had an impact on the ADNP expression of her offspring, regardless of their own VIP genotype. These results showed that VIP regulated brain ADNP expression in a regionally specific manner and indicated that both maternal and offspring VIP genotype may influence ADNP expression in the brain.
血管活性肠肽（VIP）是胚胎发生神经管闭合期发育的重要介质，可能部分调节活性依赖神经保护蛋白（ADNP）的表达，而ADNP对神经管闭合和胚胎发生至关重要。为了评估体内VIP表达对ADNP及相关蛋白ADNP2的影响，本研究检测了VIP缺陷型母亲（VIP+/-）的成年野生型（VIP +/+）和VIP基因敲除（VIP -/-）子代的基因表达，并将其与野生型母亲的野生型子代进行比较。使用ABI Prisma循环仪进行的定量实时聚合酶链反应（PCR）显示，与野生型母亲的野生型子代大脑相比，VIP基因敲除小鼠大脑中ADNP mRNA存在区域特异性减少。VIP基因敲除小鼠的皮质和下丘脑ADNP显著减少，但海马体或丘脑未减少。ADNP2表现出类似模式，但仅在下丘脑达到统计学显著减少。VIP基因敲除小鼠的野生型同窝仔的皮质和海马体中ADNP和ADNP2的mRNA也有减少趋势，这表明母亲的VIP基因型可能对其后代的ADNP表达有影响，无论其自身的VIP基因型如何。这些结果表明，VIP以区域特异性方式调节大脑ADNP表达，并表明母体和子代的VIP基因型可能影响大脑中的ADNP表达。
