Dogs have been a very useful and informative model system for human diseases for a number of reasons. Their genome is more highly conserved at the nucleotide level with human than is that of the mouse. Because certain purebred dogs are susceptible to complex diseases that also plague humans, it is possible to identify risk alleles for diseases that have not been tractable by standard human linkage studies. The dog's large body size makes tissue and fluid sampling easier, and more approximates the human for surgical approaches and imaging analyses. The rate at which dogs clear and metabolize drugs is also very similar to humans. The non-purebred population, common as household pets, is outbred and as highly diverse as the general human population, and shares many aspects of life style and environment with their human counterparts. Despite these many advantages and the recent sequencing of the dog genome, it has been difficult to produce transgenic dogs using the techniques that are so common for rodents.
In 2009, a group mainly from the College of Veterinary Medicine of Seoul National University, led by Dr. Byeong Chun Lee, described a novel transgenesis procedure adapted for dogs that uses a virus-driven gene insertion method in somatic cells that is then followed by somatic cell nuclear transfer. This method was used to generate a red fluorescent protein transgenic beagle line as proof of principle (Hong et al., genesis 47:314). In this issue, this group has refined the approach to develop a line of beagles in which expression of an eGFP transgene is inducible by feeding the animal low levels of doxycyclin. While inducible transgenes have been used extensively in rodents by crossing two transgenic lines carrying either the transactivator or the target gene, it has not been adapted to large animals that take a long time to reach puberty and have a long gestation. Instead, Kim et al. designed a vector that contains both a driver and a target transgene. They demonstrate in this report that the transgene was expressed at high levels within 2 weeks of doxycyclin treatment and returned to very low levels 3 weeks after removal of doxycyclin from the diet. Further, the transgene was detected in 3 of 4 offspring of the transgenic founder female, demonstrating efficient germ line transmission. With this technology in hand, it will now be possible to develop novel canine models to study several genetic diseases shared with humans.