NHLBI Transgenic Core

National Heart, Lung, And Blood Institute

Investigators

Linked publications & trials

Abstract

Our core was established to assist NHLBI laboratories to generate genetically engineered mouse models for better understanding basic biology as well as for modeling human genetic diseases. Now, this mission has expanded to seven other NIH institutes through signing MOUs (Memorandum of Understandings). In the past one and a half decade, genome engineering technologies have been advancing at a very rapid pace, and our core has devoted a substantial portion of our efforts on keeping up with the latest developments and adapting them to the animal model field. These include the zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR) and related Base-editing and Prime-editing technologies. In addition, through collaborations with relevant laboratories, we have made novel contributions to advance the in vivo gene-editing field. In the past year, our core successfully generated several dozens of transgenic overexpression, gene knockout and knockin mouse lines, including some sophisticated conditional knockouts, large-gene insertions, and mouse gene humanization projects. Most of these projects were completed using cutting edge CRISPR/Cas9 technologies, but we have been continuing to offer services using conventional genetic engineering and embryo micromanipulation methods, including generating transgenic mice using pronuclear microinjection, rederiving/resurrecting mouse lines using in vitro fertilization, and assessing stem cell differentiation propensities through teratoma formation assays. In addition, we have also spent a significant portion of our time and efforts on developing new capabilities, including exploring methods of using viral vectors for correcting genetic defects in mammalian cells. Together, these efforts have led to more than one dozen co-authored publications for our core staff.