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Transgenic Model Of Huntington's Disease Developed

By Staff

{image- www.boldsky.com} Researchers at the Yerkes National Primate Research Center, Emory University, have reported the development of the first transgenic nonhuman primate model of Huntington's disease (HD), a debilitating human neurodegenerative disease.

The breakthrough would help the researchers to better understand the mechanism behind HD and would also help them in developing therapies targeted to cure this disease.

And above all, this development may pave the way to the development of nonhuman primate models of other genetic diseases.

HD is a genetic, neurodegenerative disorder leading to uncontrolled movements, loss of mental processing capabilities and emotional disturbances. The disease takes its toll on patients within 10 to 15 years of the onset of the symptoms.

"In the past, researchers have used transgenic mouse models to study the disease. These models do not completely parallel the brain changes and behavioral features observed in humans with HD, thus making the development of a transgenic nonhuman primate model critical to currently treating and ultimately preventing the disease," Nature quoted lead researcher Anthony W.S. Chan, DVM, PhD, as saying.

For the study, the researchers produced the HD transgenic rhesus macaques by first injecting 130 mature oocytes with a lentivirus expressing the mutant htt gene with expanded polyglutamine repeats, which is the primary cause of HD, and a lentivirus expressing a green fluorescent protein (GFP) gene.

Next, they fertilised the oocytes by intracytoplasmic sperm injection (ICSI); and transferred 30 embryos into eight surrogates.

Later these six pregnancies and five live births (two sets of twins and one singleton) were observed, all of which had the mutant htt and GFP genes. In fact, two of these still survive.

"The transgenic monkeys are providing us with unparalleled opportunities for behavioral and cognitive assessments that mirror the assessments used with humans. With such information, much of which we are obtaining by using the Yerkes Research Center's extensive imaging capabilities, we are developing a more comprehensive view of the disease than currently available," noted Chan.

This team is one of the many teams at Yerkes, which aimed at finding the genetic basis of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases.

According to the researchers, the progress of transgenic monkeys promises future development of transgenic nonhuman primate models of other neurodegenerative diseases, such as Alzheimer's.

"The development of all such models is invaluable for understanding disease pathogenesis and for developing early diagnostic and treatment strategies," said one of the authors of the study.

The study is reported in the latest Advance Online Publication of Nature

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Story first published: Wednesday, May 21, 2008, 12:35 [IST]
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