Monkeys, New Lab Rats

New Delhi: Mice are facing competition from monkeys as the animal of choice in genetic engineering tests to determine how diseases such as Huntington’s—a fatal disorder—and muscular dystrophy are passed on.

Gene integration: (1) Hisui, (2) Wakaba, (3) Kei (left) and Kou, and (4) Banko are five transgenic marmoset offspring. When observed in ultraviolet light, the skin on the soles of their feet glows green. E SasakiJapanese scientists have been able to breed genetically engineered monkeys that can pass on their artificially inherited genes to their offspring, says a report in the next issue of Nature.

This means colonies of primates expressing a particular gene can be bred and they may serve as more accurate animal models for genetically acquired diseases that plague humans. Unlike mice, primates are genetically much closer to humans.
Erika Sasaki, of the Central Institute for Experimental Animals at Kawasaki in Japan, and her colleagues used viral DNA (deoxyribonucleic acid) as a delivery vehicle to introduce the gene for the green fluorescent protein (GFP) into the DNA of the common marmoset, a primate species found in South America.
Because it lights up when exposed to green light, scientists can easily check if the GFP gene is carried on to future generations. Sasaki’s team showed that the gene was completely integrated into the monkey’s DNA and successfully carried on to its offspring.
Though marmosets aren’t genetically as close to humans as apes and macaques are, they are much better models than rodents, say scientists.
“Genetic and physiological differences between primates and mice—including their neurophysiological functions, metabolic pathways and drug sensitivities—hamper the extrapolation of results from mouse disease models to direct clinical applications in humans...in particular, genetically-modified primates would be a powerful human disease model for preclinical assessment of the safety and efficacy of stem-cell or gene therapy,” the authors say in their report.
Unlike other primates, marmosets have short gestation periods, reach sexual maturity within a year and can produce up to 80 babies, compared with the 10 a rhesus macaque can produce, all of which make them ideal candidates for modelling the progress of a disease.
The scientists have already identified disease targets. “Our first target is Parkinson’s disease and probably Huntington’s disease,” Sasaki said in a conference call with reporters.
Experts call it a big step forward. “It’s certainly a significant achievement,” said Vinod Scaria, a researcher at the Delhi-based Institute of Genomics and Integrative Biology, a government body.
Scaria is part of an Indian project that’s scanning the zebrafish genome to look for genes that cause human disease. “The big roadblock to using primates was that it was hard to pass on genes onto germ lines (the sex cells). That’s why we are making do with mice and zebrafish, which produce many progeny.”
R. Medhamurthy, convener of the primate research centre at the Indian Institute of Science, Bangalore, said the study was “exciting”, but it was unlikely that mice would be done away with any time soon. “While this certainly means better models for diseases, it’s not easy procuring primates and monkeys for research. Mice are easy to get and because they’ve been used for so many years, there are several standard protocol that govern tests. This is a big step forward, but we have to see how wieldy this technique of using viral DNA is.”

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