Of mice and <scp>CRISPR</scp>

The usefulness of a specific technology often hits a ceiling based on technical limitations. Then, a single advance, frequently orthogonal to the core methodology, dramatically expands the utility of this technology. The effectiveness of early surgeons wielding a scalpel was severely limited by how much a patient could withstand the pain of an operation. Anesthesia was the core discovery that permitted surgery to become a consistently effective medical intervention. Molecular cloning was a powerful technology to understand the importance of genes in biology, but it had limited utility in population genetics and in medicine, because of the arduous requirements for cloning a single gene. The invention of polymerase chain reaction dramatically expanded the utility of molecular biology into high‐throughput sequencing, epidemiology, forensics, diagnostics, and gene therapy. We believe that the advent of powerful gene editing technologies such as the CRISPR/CAS system will be this transformative technology for murine genetics. The subsequent massive sequencing efforts to define the mutational spectrum of human diseases have uncovered a bewildering number of genetic changes. It is now recognized that most diseases are genetically complex and that their dissection requires the enrollment of many hundreds of thousands of individuals to achieve adequate statistical power to ensure the validity of an association. This purely statistical approach is clearly impracticable, given the many variants and mutations that are being uncovered with each sequence‐based study. Thus, the translation of human genome research into health care heavily relies on appropriate organismal models that accurately reflect the human condition. This is where the laboratory mouse ( Mus musculus ) comes in. For many diseases that require an intact organ system in an intact animal—such as neurological disorders, renal disease, complex cardiopulmonary syndromes, and aging—the mouse has been a primary experimental model for mammalian biology since the turn of the last century. &gt; … …