Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain
Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain
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DOI：
10.1101/gad.862101
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发表时间：
2001-04-01
影响因子：
10.5
通讯作者：
Parada, LF
中科院分区：
文献类型：
--
作者：
Zhu, Y;Romero, MI;Parada, LF
1型神经纤维瘤病（NF 1）是一种影响神经嵴源性细胞群生长特性的常见遗传性疾病。此外，大约一半的NF 1患者表现出学习障碍。为了表征NF 1在体外和体内的功能，我们通过使用Cre/loxP技术在NF 1基因中产生条件性突变来规避NF 1缺失小鼠胚胎的胚胎致死性。将突触蛋白I启动子驱动的Cre转基因小鼠品系引入到条件性NF 1背景中在大多数分化的神经元群体中具有消融的NF 1功能。这些小鼠的大脑皮层发育异常，这表明NF 1在CNS发育的这一方面具有不可或缺的作用。此外，尽管它们是无肿瘤的，但这些小鼠在不存在明显的神经变性或小胶质细胞增生的情况下显示出广泛的星形胶质细胞增生。这些结果表明，NF 1缺陷的神经元能够通过非细胞自主机制诱导反应性星形胶质细胞增生。
Neurofibromatosis type 1 (NF1) is a prevalent genetic disorder that affects growth properties of neural-crest-derived cell populations. In addition, approximately one-half of NF1 patients exhibit learning disabilities. To characterize NF1 function both in vitro and in vivo, we circumvent the embryonic lethality of NF1 null mouse embryos by generating a conditional mutation in the NF1 gene using Cre/loxP technology. Introduction of a Synapsin I promoter driven Cre transgenic mouse strain into the conditional NF1 background has ablated NF1 function in most differentiated neuronal populations. These mice have abnormal development of the cerebral cortex, which suggests that NF1 has an indispensable role in this aspect of CNS development. Furthermore, although they are tumor free, these mice display extensive astrogliosis in the absence of conspicuous neurodegeneration or microgliosis. These results indicate that NF1-deficient neurons are capable of inducing reactive astrogliosis via a non-cell autonomous mechanism.