Protein and gene expression analysis of Phf6, the gene mutated in the Borjeson-Forssman-Lehmann Syndrome of intellectual disability and obesity
Protein and gene expression analysis of Phf6, the gene mutated in the Borjeson-Forssman-Lehmann Syndrome of intellectual disability and obesity
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DOI：
10.1016/j.modgep.2007.06.007
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发表时间：
2007-10-01
影响因子：
1.2
通讯作者：
Thomas, Tim
中科院分区：
文献类型：
--
作者：
Voss, Anne K.;Gamble, Robin;Thomas, Tim
植物同源结构域指基因6（PHF 6）被鉴定为在患有Borjeson-Forssman-Lehmann综合征（BFLS）（一种X连锁精神发育迟滞障碍）的患者中突变的基因。BFLS精神残疾从很小的时候就很明显，这表明大脑发育缺陷。PHF 6蛋白含有四个核定位信号和两个不完美的植物同源结构域（PHD）的手指类似的第三，不完美的PHD手指的成员的三胸家族的转录调节因子。PHF 6基因在脊椎动物中高度保守。尽管PHF 6基因突变的破坏性影响，但对PHF 6的细胞功能一无所知。为了奠定基础的功能研究，我们确定在这里的细胞类型，表达鼠Phf 6基因和蛋白质在产前和产后的发展。Phf 6基因和蛋白广泛表达。然而，表达水平从强到几乎检测不到不等。在发育中的中枢神经系统、垂体前叶、面部结构的原基和肢芽中观察到最强的Phf 6基因表达和Phf 6蛋白的核定位。mRNA和蛋白质的表达水平在发育过程中下降。在成人大脑中，适度的Phf 6表达维持在投射神经元中，例如嗅球中的二尖瓣细胞、皮质锥体细胞和小脑浦肯野细胞。Phf 6基因表达和Phf 6蛋白的核定位与BFLS患者的临床症状相关，即精神残疾、全垂体前叶激素缺乏和面部以及手指异常。(c)2007 Elsevier B. V.保留所有权利。
The Plant homeodomain finger gene 6 (PHF6) was identified as the gene mutated in patients suffering from the Borjeson-Forssman-Lehmann Syndrome (BFLS), an X-linked mental retardation disorder. BFLS mental disability is evident from an early age, suggesting a developmental brain defect. The PHF6 protein contains four nuclear localisation signals and two imperfect plant homeodomain (PHD) fingers similar to the third, imperfect PHD fingers in members of the trithorax family of transcriptional regulators. The PHF6 gene is highly conserved in vertebrate species. Despite the devastating effects of mutation of the PHF6 gene, nothing is known about the cellular function of PHF6. In order to lay the base for functional studies, we identify here the cell types that express the murine Phf6 gene and protein during prenatal and postnatal development. The Phf6 gene and protein are expressed widely. However, expression levels vary from strong to barely detectable. Strongest Phf6 gene expression and nuclear localisation of Phf6 protein were observed in the developing central nervous system, the anterior pituitary gland, the primordia of facial structures and the limb buds. Expression levels of both mRNA and protein decline over the course of development. In the adult brain moderate Phf6 expression is maintained in projection neurons, such as mitral cells in the olfactory bulb, cerebrocortical pyramidal cells and cerebellar Purkinje cells. Phf6 gene expression and nuclear localisation of Phf6 protein correlate with clinical symptoms in BFLS patients, namely mental disability, pan-anterior pituitary hormonal deficiency and facial as well digit abnormalities. (c) 2007 Elsevier B.V. All rights reserved.