MeCP2转基因食蟹猴所表征的类自闭症行为及种系传递

 自闭症是近年来公众关注度很高的一种神经系统疾病，甲基化CpG结合蛋白2（MeCP2）因其能够在转录水平调节基因表达和操控微小RNA（miRNA）的效应而在自闭症中扮演着重要的角色。当MeCP2因突变而功能缺失时会导致瑞特综合症（Rett syndrome），而当MeCP2拷贝数过多则会导致一种名为MeCP2重复综合症的自闭症。虽然目前科学家已经构建成功了MeCP2的转基因小鼠，但在这种小鼠模型中无法很好地观察到类似人类自闭症的表型。本研究组通过慢病毒侵染的方法构建了能在神经系统中特异表达人源MeCP2的转基因食蟹猴模型，并通过深度测序检测出了转基因插入位点以及通过免疫印迹（westernblot）确证了外源基因的表达。该转基因食蟹猴模型在行动、社交及情绪方面表现出明显的类似自闭症行为，并呈现转基因的种系传递现象。这些结果表明通过基因编辑技术构建非人灵长类模型在脑疾病研究中的重要性。     

Expression of chromatin modification genes in organs of cloned cattle that died within hours after birth

Several mammalian species including sheep[1,2], bo- vine[3], goats[4], mice[5], pigs[6], cat[7] and rabbits[8], have been successfully cloned by somatic nuclear transfer (NT), but the efficiency of this process is poor, with only a small proportion of the…     

人类新基因SEC15L3 cDNA的鉴定

从人胎脑cDNA文库中克隆到1条新的Sec15基因SEC15L3 cDNA,比已报道的SEC15L1(NM_019053)少4个外显子,并已提交GenBank,登录号为EF571007.RT-PCR和荧光定量PCR实验显示该基因在胰腺、脾脏、胸腺、前列腺和睾丸几个组织中表达量较高,而且与SEC15L1的组织表达谱有明显差异.生物信息学方法模拟SEC15L3蛋白,并与SEC15L1比较,结果显示两者有不同的高级结构,已推测出两者可能是不同exocyst的成分,并且在不同组织中行使不同功能.     

Premature ageing in mice expressing defective mitochondrial DNA polymerase

Point mutations and deletions of mitochondrial DNA (mtDNA) accumulate in a variety of tissues during ageing in humans, monkeys and rodents. These mutations are unevenly distributed and can accumulate clonally in certain cells, causing a mosaic pattern of respiratory chain deficiency in tissues such as heart, skeletal muscle and brain. In terms of the ageing process, their possible causative effects have been intensely debated because of their low abundance and purely correlative connection with ageing. We have now addressed this question experimentally by creating homozygous knock-in mice that express a proof-reading-deficient version of PolgA, the nucleus-encoded catalytic subunit of mtDNA polymerase. Here we show that the knock-in mice develop an mtDNA mutator phenotype with a threefold to fivefold increase in the levels of point mutations, as well as increased amounts of deleted mtDNA. This increase in somatic mtDNA mutations is associated with reduced lifespan and premature onset of ageing-related phenotypes such as weight loss, reduced subcutaneous fat, alopecia (hair loss), kyphosis (curvature of the spine), osteoporosis, anaemia, reduced fertility and heart enlargement. Our results thus provide a causative link between mtDNA mutations and ageing phenotypes in mammals.     

Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18

Excitatory amino-acid carrier 1 (EAAC1) is a high-affinity Na+-dependent L-glutamate/D,L-aspartate cell-membrane transport protein. It is expressed in brain as well as several non-nervous tissues. In brain, EAAC1 is the primary neuronal glutamate transporter. It has a polarized distribution in cells and mainly functions perisynaptically to transport glutamate from the extracellular environment. In the kidney it is involved in renal acidic amino-acid re-absorption and amino-acid metabolism. Here we describe the identification and characterization of an EAAC1-associated protein, GTRAP3-18. Like EAAC1, GTRAP3-18 is expressed in numerous tissues. It localizes to the cell membrane and cytoplasm, and specifically interacts with carboxy-terminal intracellular domain of EAAC1. Increasing the expression of GTRAP3-18 in cells reduces EAAC1-mediated glutamate transport by lowering substrate affinity. The expression of GTRAP3-18 can be upregulated by retinoic acid, which results in a specific reduction of EAAC1-mediated glutamate transport. These studies show that glutamate transport proteins can be regulated potently and that GTRAP can modulate the transport functions ascribed to EAAC1. GTRAP3-18 may be important in regulating the metabolic function of EAAC1.