CRISPR/Cas9‐Mediated Rescue of Shiverer Mice (MBPShi) via AAV9 Delivery across the Blood‐Brain Barrier

Abstract

The shiverer mouse is a genetically modified strain of M. musculus which exhibits ataxia, tremor, and seizure, among other symptoms, due to impaired CNS function. The strain is generated through deletion of a large portion of the Myelin Basic Protein (MBP) gene. Due to lack of MBP, the shiverer mouse presents with hypomyelination and the corresponding “shivering” phenotype. To date, shiverer mouse rescue has been accomplished through embryological stem‐cell implant, or gene delivery via zygote microinjection. However, these methods are limited to rescue of the subsequent generation and cannot be applied to a mouse of the current generation. Another obstacle to consider when exploring pathologies affecting the CNS is the ability of a therapeutic candidate to cross the blood‐brain barrier (BBB). Here we propose a novel method for the genetic rescue of current‐generation shiverer mice. This method involves CRISPR‐mediated insertion of a functional MBP transgene via the delivery of an AAV9 delivery mechanism. This involves a simple procedure of non‐specific intravenous injection of the mouse, relying on viral delivery across the BBB and bypassing the need for invasive surgical intervention.Support or Funding InformationD'Youville CollegeThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.