博文

NC——科学家开发中枢外细胞系删除技术

已有 2694 次阅读 2017-4-29 23:18 |个人分类:神经科学临床和基础|系统分类:观点评述| 技术, 科学家, style, 开发, 细胞系

NC——科学家开发中枢外细胞系删除技术

简介

在细胞上表达白喉毒素受体，可以特异性的删除某类细胞，比如在GABA能神经元上表达DTR，然后在给予DT之后就会导致该类神经元的丢失。但是最近科学家找到了一种方法，可以只删除外周的细胞系，而对中枢内的细胞系没有影响。以下是摘要：
Conditional expression of diphtheria toxin receptor (DTR) is widely used for tissue-specific ablation of cells. However, diphtheria toxin (DT) crosses the blood–brain barrier, which limits its utility for ablating peripheral cells using Cre drivers that are also expressed in the central nervous system (CNS). Here we report the development of a brain-sparing DT, termed BRAINSPAReDT, for tissue-specific genetic ablation of cells outside the CNS. We prevent blood–brain barrier passage of DT through PEGylation, which polarizes the molecule and increases its size. We validate BRAINSPAReDT with regional genetic sympathectomy: BRAINSPAReDT ablates peripheral but not central catecholaminergic neurons, thus avoiding the Parkinson-like phenotype associated with full dopaminergic depletion. Regional sympathectomy compromises adipose tissue thermogenesis, and renders mice susceptible to obesity. We provide a proof of principle that BRAINSPAReDT can be used for Cre/DTR tissuespecific ablation outside the brain using CNS drivers, while consolidating the link between adiposity and the sympathetic nervous system.