microRNAs have often been referred to as the “Dark Matter” of the genome, and their surprising discovery has completely changed our concept of how complex organisms develop and function. We have an ambitious effort to ablate >100 evolutionarily conserved noncoding RNA genes in the mouse, using an advanced strategy to genetically modify embryonic stem cells.
Our project will make a great impact by shedding insight into the in vivo role of these tiny but important genes. We are making all the generated microRNA transgenic ES cells and mouse reagents freely available to the academic scientific community, which will meet a compelling need in the field of genetics. We are presently developing a website that will aid their dispersal and will coordinate and subcontract with a specialized mouse distribution center, such as the NIH and Jackson Labs.
It is important to note that microRNAs may be expressed in many tissues. Investigators will use the conditional knockout mice to study microRNA function in many systems, such as the brain, immune, pancreas, heart, etc. Thus we expect our project will create a significant and long-lasting impact, and yield reagents and novel technologies of broad use throughout the scientific community. Because of the sheer novelty of these knockouts, it is difficult to anticipate the range and nature of the phenotypes. However, based on the predicted functions of miRNAs, we anticipate that the phenotypes will be rich, and cause many conventional “protein-centric” investigators to rethink the origin and mechanisms of human disease. As such we believe this project has the capacity to touch many lives, from investigators of basic biology and medicine to those plagued with devastating disease of unknown etiology. This work is funded by the NIH and the W.M. Keck Foundation.