Cre-driver rat resource project R24

Medical College Of Wisconsin, Milwaukee WI

Investigators

Abstract

PROJECT SUMMARY This R24 resource grant will leverage our existing infrastructure: personnel, expertise in rat transgenesis and gene editing, high throughput strain development and characterization, cryopreservation and rederivation, and distribution channels resulting in an economy of scale to generate novel and important Cre-driver rat models for the research community through the following three aims. Aim 1) Establish the utility of existing Cre-driver rat models of potentially high biomedical research interest. Models already created by others in the field with particularly high value to multiple investigators, but with lack of characterization data will be imported and initially validated by crossing with a Cre-sensitive fluorescent reporter model to characterize the on-target and off-target tissue specificity and reproducibility of each model. Another goal of Aim 1 will be do develop and test new Cre-sensitive reporter strains with bioluminescent reporters to allow in vivo imaging of Cre-driver activity. Aim 2) Develop additional Cre-driver and floxed gene model strains to broadly impact the research community. We will solicit applications from the community of rat model investigators in the field to create and characterize additional high value, novel transgenic Cre-driver models for tissues relevant to multiple research investigators. Investigators may also propose to develop a floxed gene model critical to their studies. An externally led scientific review process will be used identify the largest need and most broadly useful models for development. Models will be developed using cutting edge approaches and characterized as in Aim 1. Aim 3) Gather Cre-driver strain data under one community supported Cre-driver rat resource to be hosted by the Rat Genome Database. Data collected in Aims 1 and 2 and from Cre models developed and published by other research groups will be curated by our team and hosted in the Rat Genome Database to establish a one-stop searchable Cre-driver rat resource portal. Together, these aims to characterize and develop new Cre-driver rat strains and collect and share all models and data in a single Cre-driver rat data resource will benefit the broad research community using this species by identifying the models which are most needed, filling gaps in research areas lacking these tools, and developing these models in a cost-effective way to establish a critically lacking set of tools for these researchers.