| First Author | Pereira MM | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 14967 | PubMed ID | 28367972 |
| Mgi Jnum | J:296542 | Mgi Id | MGI:5921647 |
| Doi | 10.1038/ncomms14967 | Citation | Pereira MM, et al. (2017) A brain-sparing diphtheria toxin for chemical genetic ablation of peripheral cell lineages. Nat Commun 8:14967 |
| abstractText | 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 tissue-specific ablation outside the brain using CNS drivers, while consolidating the link between adiposity and the sympathetic nervous system. |
