Venhoranta Heli, Bauersachs Stefan, Taponen Juhani, Lohi Hannes, Taira Tomi, Andersson Magnus, Kind Alexander, Schnieke Angelika, Flisikowski Krzysztof
Department of Production Animal Medicine, University of Helsinki, Saarentaus, Finland.
Int J Dev Neurosci. 2013 Nov;31(7):463-7. doi: 10.1016/j.ijdevneu.2013.05.003. Epub 2013 May 29.
We examined levels of gene expression in the brains of bovine fetuses carrying a truncated MIMT1 allele, MIMT1(Del), shown to cause late abortion and stillbirth as a result of fetal growth restriction. MIMT1 is a non-protein coding gene that forms part of the imprinted PEG3 (paternally expressed gene 3) domain. Microarray analysis of brain cortex samples from mid-gestation MIMT1(Del/WT) bovine fetuses and wild-type siblings was performed to study the effect of fetal growth restriction on brain gene expression. Statistical analysis revealed 134 genes with increased mRNA levels and 22 with reduced levels in MIMT1(Del/WT) fetuses. Gene set enrichment analysis identified a relatively small number of significant functional clusters representing three major biological processes: response to oxidative stress, angiogenesis, and epithelial cell proliferation. Gene expression microarray analyses identified increased expression of VIPR2, HTRA1, S100A4 and MYH8 in fetuses carrying the deletion and decreased expression of DRD2, ADAM18, miR345, ZNF585A. ADAM18, DRD2 and S100A4 are known to be involved in prenatal brain development. ZNF585A, miR-345, VIPR2, HTRA1, and MYH8 are known to be involved in cell growth and differentiation, but any role in neural developmental has yet to be elucidated.
我们检测了携带截短型MIMT1等位基因MIMT1(Del)的牛胎儿大脑中的基因表达水平，该等位基因已证明会因胎儿生长受限导致晚期流产和死产。MIMT1是一个非蛋白质编码基因，是印记PEG3（父源表达基因3）结构域的一部分。对妊娠中期MIMT1(Del/WT)牛胎儿和野生型同胞的大脑皮质样本进行微阵列分析，以研究胎儿生长受限对大脑基因表达的影响。统计分析显示，MIMT1(Del/WT)胎儿中有134个基因的mRNA水平升高，22个基因的水平降低。基因集富集分析确定了相对较少数量的显著功能簇，代表三个主要生物学过程：对氧化应激的反应、血管生成和上皮细胞增殖。基因表达微阵列分析确定，携带缺失的胎儿中VIPR2、HTRA1、S100A4和MYH8的表达增加，而DRD2、ADAM18、miR345、ZNF585A的表达降低。已知ADAM18、DRD2和S100A4参与产前脑发育。已知ZNF585A、miR-345、VIPR2、HTRA1和MYH8参与细胞生长和分化，但它们在神经发育中的任何作用尚未阐明。
