REELIN DEFICIENCY--MODEL FOR SCHIZOPHRENIA VULNERABILITY

描述：（改编自研究者摘要）端脑 已知结构遵循异常复杂的胚胎学过程， 在这一过程中，ODN发挥着关键的信号作用。本课题 想要确定是否在出生后和成年小鼠中遗传性地缺乏BDN (RELN单倍不足）导致进行性和 特定区域的大脑异常以及某些异常 类似于在精神分裂症患者大脑中观察到的变化的漫画 患者我们选择了杂合子reeler突变（rl +/-）小鼠作为研究对象。 单倍不足模型。在初步实验中，我们已经表明， 在成年rl +/-小鼠中，除了存在低于正常的cDNAN表达外， 存在许多显微解剖和神经生理异常 精神分裂症的症状因此，我们建议：1）比较是否 表达和神经元定位在R1 +/-和野生型（WT）小鼠中相似; 2)确定是否在细胞中存在cDNAN单倍性不足的改变， 存在的关系之间的单倍功能不全和改变皮质 GABA能中间神经元的分布，GAD 67表达的减少， 神经元密度降低; 3）研究是否有进展，这些 随着年龄的变化，或者如果这些变化仅限于皮质或存在 在精神分裂症中也受到影响的其他大脑区域;以及4）检查是否 JNK单倍不足是一个易受影响的因素， 小鼠的行为和显微解剖异常的发病率， 暴露于有害的侮辱，如社会孤立压力。 虽然推测的CINN单倍不足与表观遗传的相互作用 精神分裂症患者中发生的因素可能与这些因素不同， 在社会隔离的小鼠中，对小鼠模型的研究可能揭示这些 神经发育的机制，可能会被破坏， 精神分裂症患者大脑中的缺陷。对ODN的理解 成年人大脑中的表达调控可能在设计中非常重要， 药理学工具，以纠正脑功能不全， 与这种缺陷相关的行为和显微解剖学异常。

DESCRIPTION: (Adapted from the Investigator's Abstract) Telencephalic brain structures are known to follow an unusually complex course of embryological developmental in which RELN plays a pivotal signaling role. In this project, we want to establish whether in postnatal and adult mice genetic RELN deficiency (RELN haploinsufficiency) leads to the expression of progressive and region-specific brain abnormalities and whether some of the abnormalities resemble caricatures of the alterations observed in the brain of schizophrenic patients. We have selected the heterozygous reeler mutant (rl +/-) mouse as a model of RELN haploinsufficiency. In preliminary experiments we have shown that in adult rl +/- mice, in addition to a lower than normal RELN expression there are a number of microanatomical and neurophysiological abnormalities reminiscent of schizophrenia. Thus, we propose to 1) compare whether RELN expression and neuronal location are similar in rl +/- and wild-type (wt) mice; 2) determine whether RELN haploinsufficiency elicits changes in the relationship existing between RELN haploinsufficiency and altered cortical distribution of GABAergic interneurons, decrease of GAD67 expression and decrease in neuropil density; 3) study if there is a progression of these changes with age, or if these changes are restricted to cortex or are present in other brain areas that are also affected in schizophrenia; and 4) examine if RELN haploinsufficiency is a vulnerability factor that predisposes peripubertal mice to an incidence of behavioral and microanatomical abnormalities when exposed to noxious insults such as social isolation stress. Although the putative interaction of RELN haploinsufficiency with epigenetic factors occurring in schizophrenic patients probably differs from the factors operative in socially isolated mice, study of the murine model may reveal those mechanisms of neurodevelopment that are likely to be disrupted by RELN deficiency in the brain of schizophrenic patients. The understanding of RELN expression regulation in adult brain may be of great importance in the design of pharmacological tools to correct RELN brain insufficiency and to reduce the behavioral and microanatomical abnormalities associated to this deficiency.