NHLBI Transgenic Core

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

The main mission of our core is to assist NIH scientists in generating genetically engineered animal models to support their scientific research. Genome engineering technologies have been advancing very rapidly in the past decade, especially the so-called CRISPR (clustered regularly interspaced short palindromic repeat) method has dramatically changed the way animal models are created. In the past several years, our core has spent a significant portion of our efforts on keeping up with the latest technological developments and efficiently applying them to animal model generation. COVID-19 has obviously had a negative impact on our cores operation. During the entire fiscal year, only 50% of our staff time was permitted to work on campus. Under this difficult situation, we have managed to successfully generate more than two dozen knockout/knockin mouse lines, and coauthored over one dozen publications. We have been continuingly offer a variety of services using our cores expertise and special instrumentation in the area of gene-editing, embryo micromanipulation, and assisted reproduction technologies, including generating transgenic mice by pronuclear microinjection, generating knockout/knockin mice using the classical homologous recombination-mediated methods as well as the newer nuclease-mediated genome engineering technologies, re-deriving/resurrecting mouse lines using in vitro fertilization, and assessing stem cell differentiation propensities through teratoma formation assays. CRISPR technology has greatly simplified the processes for generating knockout and small knockin animal models, but it still remains challenging to generate conditional knockout (cKO) and large knockin mice. Some of these projects require multi-stepped genetic manipulations, which often require breeding up the intermediate mice in order to produce the large number of zygotes needed for the next round of microinjection. In the past several years, we have devoted a significant portion of our efforts on optimizing conditions and streamlining procedures for reducing animal costs and increasing productivity. Our core is also actively developing capabilities for using gene-editing technologies in adult animals for making animal models supporting basic research and for validating therapeutic approaches.