For the first time, scientists in Japan have genetically modified a monkey so that it passes on the foreign gene to its offspring, in an advance that holds promise for modelling genetic diseases.
The researchers used viral DNA to deliver a gene coding for green fluorescent protein (GFP) into the DNA of embryos of marmosets, New World primates. Those embryos that expressed GFP were then selected for implantation in surrogate mothers, which subsequently produced five transgenic offspring. The animals glowed green, confirming that the gene for GFP was incorporated into their genomes and expressed in various tissues.
Moreover, the gene was incorporated into the reproductive cells of two of the offspring and, following IVF of a normal marmoset egg with sperm from one of the transgenic animals, was passed down to a second generation of marmosets, which also glowed green and were healthy. This is the first time that transgenic primates have been obtained through germline transmission (Nature 2009, 459, 515).
The results suggest that transgenic marmosets could be used as experimental animals for biomedical research, say the researchers. Mouse models of disease are common research tools but, because primates are more functionally and anatomically similar to humans, it is hoped that primate models will enhance research in certain areas, such as brain disorders, that have proven difficult to replicate in mice. ‘Our next step is applying these techniques to neuroscience to understand or develop new therapies for neuronal disorder disease,’ says Erika Sasaki, laboratory head of the Central Institute of Experimental Animals in Japan, who led the research.
However, Gerald Schatten, from the University of Pittsburgh School of Medicine, US, and Shoukhrat Mitalipov, from the Oregon National Primate Research Center, US, point out that marmosets have limitations as research models. For example, biological differences mean that HIV/AIDS and TB can only be studied in Old World primates such as baboons.
Moreover, addressing potential animal welfare concerns, Schatten and Mitalipov suggest that scientists might direct research primarily at incurable diseases for which there are potential preclinical-stage treatments, before colonies of primate disease models are established (Nature 2009, 459, 515).
Helen Wallace, executive director of GeneWatch UK, says proposals to create generations of marmosets that suffer from genetic disorders raise serious ethical issues. ‘Future attempts to genetically engineer humans in this way would be a dangerous and unjustifiable experiment on mothers and their babies.’
Schatten and Mitalipov say that scientists need to engage with the public in an informed bioethical debate about genetic modifications and innovation in reproductive biology.