Of Men and Mice: Lots and Lots of Mice

Abstract

Sometimes we are victims of our own success. A case in point is transgenic mice. Not so long ago, the notion of selecting a gene and deleting it in a living mouse seemed like science fiction, but now knocking out specific genes in mice is a routine procedure. Some centers have produced literally hundreds of knockout mice, and a serious effort is underway to create a knockout mouse for each of the 25,000 or so genes in the mouse genome. It does not stop here. Knock-in strategies replace genes with disease-causing alleles and insert completely foreign genes, such as green fluorescent protein from jellyfish and various viral proteins, into mouse chromosomes. Moreover, placement of inserted genes downstream of different tissue promoters directs gene expression to specific organs, such as the intestine or liver. There seems no end in sight to the proliferation of knockout and transgenic mouse strains. A real consideration is where to keep all these animals, and universities and other research institutions are scrambling to expand their facilities to accommodate the burgeoning number of transgenic mouse strains. In part, commercial vendors have taken up the slack by selling selected strains and offering other services, such as reestablishing colonies from frozen embryos, and National Institutes of Health (NIH) has funded a handful of mutant mouse centers. Nonetheless, these sources can be less than fully reliable. I recently participated in a study using a knockout mouse strain from a commercial vendor. By the time the study was completed, written up for a journal and peer-reviewed, the strain was no longer available to respond to questions raised by the reviewers. Although colonies can be reestablished from frozen embryos, the process is expensive, slow, and inadequate to meet time limits set by journals for re-submission of revised manuscripts. An underutilized resource is the simple sharing of transgenic mice between institutions. Whereas institutional animal facilities will accept immediately animals furnished by vendors like Jackson Laboratory, Charles River, Harlan and others, the same facilities will not accept animals from other accredited institutions without prolonged quarantines and other restrictions. The reason is to prevent introduction of viruses and other pathogens. Veterinarians will tell you that the increased exchange and sharing of transgenic mice has led to a resurgence of murine infectious diseases. However, if mice can be accepted from pathogen-free vendor colonies, why not from pathogen-free institutional colonies? A basic reason is the absence of an accepted standard and accreditation process to certify animal colonies of universities and other institutions as pathogen-free and qualified to ship mice just like vendors do. With certification, regional and even national consortia could be developed to share transgenic mice. By eliminating the redundancy of maintaining colonies of the same mouse strains at multiple locations, the cost savings could be considerable. By eliminating quarantines, more research could be done faster. Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) together with NIH should be encouraged to develop and institute such standards, since the link of mice to men has never been stronger.