Abstract P292: Gene Editing Rat Resource Center: Rat Models for Heart, Lung, Blood, and Sleep Disorder Studies

Transgenesis and gene editing in the rat has produced gene-modified strains which can be used to validate a gene underlying a quantitative trait locus or human association, or to design follow up studies to define function and physiological roles of genes or sequence variants. We are currently in the fifth year of developing rat models for investigators to validate human variation and study function and mechanism for genes implicated in heart, lung and blood disorders. The Gene Editing Rat Resource Center (GERRC, http://rgd.mcw.edu/wg/custom_rats/gerrc ) is an NHLBI-funded R24 resource program to generate, distribute, and cryopreserve novel rat models to the research community. Investigator-initiated applications to produce novel genetically modified rat strains were received from laboratories across the world and reviewed by an external advisory board for scientific merit and potential broad interest to the heart, lung, blood, and sleep disorder research community. Custom knockout, knockin, and transgenic rat models continue to be developed. To date, we have transferred over 19,570 microinjected embryos, resulting in 4000+ live-born pups of which 3400+ have been screened for transgenesis or mutagenesis of the target gene. Of these, we have successfully generated ~630 pups containing transgenes or targeted mutations in 95 genes, distributed among 16 inbred, outbred, consomic and congenic rat strains frequently used in cardiovascular research. After confirming germline transmission, heterozygous breeders are distributed to the requesting investigator and then each model is made available to the rat research community. Sperm is cryopreserved to maintain a permanent source of these models. Collectively, the GERRC resource represents the largest collection of genetically modified rat models which are distributable to any investigator through a standard materials transfer agreement at the cost of rearing and shipping. We will discuss the general progress of genetic engineering in rats, current challenges for the field, and opportunities for future developments.