A paper describing methods to genetically modify the domestic cat is published this week in Nature Methods. This technology will prove important for studies in neurobiology and in disease modeling.
Genetically modified cats have so far been generated by somatic cell nuclear transfer (cloning). But this process is very inefficient and even animals that look visually normal can have aberrations at the cellular and molecular level. Eric Poeschla and colleagues now describe methods for cat transgenesis using viral vectors to modify oocytes obtained from routine spaying procedures. They report efficient transgenesis, robust transgene expression, three healthy kittens and transmission of the modification to the next generation.
They then apply this approach to the study of AIDS-virus pathogenesis. Some animal species express factors that make them resistant to the AIDS-causing viruses of other species. The team generated transgenic cats expressing antiviral factors from the rhesus macaque and observed preliminarily that there is reduced feline AIDS virus replication in the cells of these cats. They caution, however, that whole-organism infection studies remain to be done.
This is the first report of genetic modification of gametes in a carnivore. Because of their size, complexity and susceptibility to AIDS-causing viruses, cats can be used for several types of studies that are not feasible in the mouse. The transgenesis reported in this study will increase the range of experiments that are possible in this model and may contribute to an increased understanding of both feline and human disease.