Patients with inherited peripheral neuropathies, such as Charcot-Marie-Tooth disease (CMT), are provided life-long supportive care, but there are currently no treatments or cures. Progress toward such treatments is slow due, in part, to the fact that there are too few animal models available to conduct research that could lead to new treatments. The rate at which new CMT disease genes/mutations are identified currently exceeds the rate at which appropriate models can be developed. There are now ~80 human CMT disease loci, including at least 60 genes, and most of these do not yet have an associated clinically-relevant animal model. To remedy this problem we propose the creation of The Resource for Research of Peripheral Neuropathy (RRPN) at The Jackson Laboratory (JAX). The JAX-RRPN (www.jax.org/rrpn) is a coordinated, community-driven effort that leverages a world-leading knowledge of mouse genetics, state-of-the-art genome editing capability, decades of experience in disease model development and experience with effective disease model repositories, to accelerate the creation, distribution and proper use of high-priority mouse models for CMT research.
The Research Resource for Peripheral Neuropathy (RRPN) will serve as a central resource for mouse models of peripheral neuropathy. While some models already exist, their accessibility is limited because the investigators who generated them do not have the infrastructure necessary to distribute them. Other models that are deposited are often encumbered with restrictions or heavy licensing fees to for-profit companies by the originating research institutions. Utilizing the existing JAX Genetic Resource Sciences Repository, the RRPN will ensure all models are available and with as few legal restrictions as possible. Models will be produced with defined neurological lesions on an optimized genetic background, cryopreserved and distributed. The RRPN will also assist in validating the efficacy of new mouse models for the disease being studied. In so doing, we will significantly increase the number of available disease models based on community-driven priority and accelerate preclinical testing of potential new treatments.
| Morelli, Kathryn H; Seburn, Kevin L; Schroeder, David G et al. (2017) Severity of Demyelinating and Axonal Neuropathy Mouse Models Is Modified by Genes Affecting Structure and Function of Peripheral Nodes. Cell Rep 18:3178-3191 |
