Model monkeys.
These two monkeys are among the first genetically modified primates with signs of human neurological disease.
Yerkes National Primate Research Center
Researchers often rely on mice to study a range of genetic diseases in the laboratory. This is not to a satisfactory approach for many neurodegenerative diseases that involve cognitive and behavioral symptoms that do not easily fit human patients on rodents. Now, in a development that opens the door to the modeling of these diseases in primates, researchers have created the first transgenic monkeys with neurological signs of Huntington's disease (HD).
HD is caused by a mutation in a gene called HTT , which triggers the degeneration of neurons in the striatum and cortex, which leads to uncontrolled muscle movements and mental disorders . Anthony Chan, a geneticist at the Yerkes National Primate Research Center of Emory University in Atlanta, Georgia, and colleagues injected the mutant HTT gene in 130 oocytes collected from rhesus monkeys before fertilize them laboratory. They implanted 30 embryos in eight female macaques. Ultimately, five have captured and survived the delivery, production line described born today in macaques Nature .
Two monkeys whose tissues showed high expression of the mutant gene suffered from breathing difficulties and other motor impairments. They died one day after birth. In their brain tissue, researchers have seen evidence of neuronal damage similar to that observed in patients with Huntington's disease. Another newborn monkey began to display involuntary movements of one week after birth and died within a month. Of the remaining two monkeys, who were aged 6 months when the authors submitted the paper, the mutant gene was expressed very little in one and at a moderate level in the other: the first is normally included so the second showed conventional HD symptoms such as jerking of limbs and twisted posture.
Chan and his colleagues are now following these two animals, using brain imaging and cognitive and behavioral tests to study disease progression. "We believe that the integration of information from these studies will help us better understand how HD develops and progresses," says Chan.
The technological prowess to design transgenic primates with a carrier gene diseases is "a tremendous advance," said Christopher Ross, neuropsychiatrist at Johns Hopkins University in Baltimore, Maryland. "The monkey phenotype closely resembles behaviorally human phenotype", which should make the primates better than mice to test drugs for Huntington, said Ross. The great hope, he says, is that the technique will one day lead to primate models of "schizophrenia and other neuropsychiatric diseases that are not easily modeled in mice." Before that, of course, researchers will sort the complex genetic contributions to these disorders.
related Site
- HD on information from the National Institute of neurological disorders and Stroke
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