We provide a proof of principle that BRAINSPAReDT can be used for Cre/DTR tissue-specific ablation outside the brain using CNS drivers, while consolidating the link between adiposity and the sympathetic nervous system.Ĭonditional expression of the diphtheria toxin receptor (DTR) using the Cre/lox system is a widely used tool for tissue-specific ablation of cells. Regional sympathectomy compromises adipose tissue thermogenesis, and renders mice susceptible to obesity. 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. We prevent blood–brain barrier passage of DT through PEGylation, which polarizes the molecule and increases its size. Here we report the development of a brain-sparing DT, termed BRAINSPAReDT, for tissue-specific genetic ablation of cells outside the CNS. 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). ![]() Conditional expression of diphtheria toxin receptor (DTR) is widely used for tissue-specific ablation of cells.
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