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First Transgenic Monkey Model Of Huntington's Disease Developed

Date:
May 19, 2008
Source:
NIH/National Center for Research Resources
Summary:
Scientists have developed the first genetically altered monkey model that replicates some symptoms observed in patients with Huntington's disease, according to a new study funded by the National Institutes of Health. Researchers are now able to better understand this complex, devastating and incurable genetic disorder affecting the brain. This advance, reported in Nature, could lead to major breakthroughs in the effort to develop new treatments for a range of neurological diseases.

A rhesus macaque monkey (similar to the one shown above) was genetically altered monkey model that replicates some symptoms observed in human patients with Huntington's disease.
Credit: iStockphoto/Nathaniel Frey

Scientists have developed the first genetically altered monkey model that replicates some symptoms observed in patients with Huntington's disease, according to a new study funded by the National Institutes of Health. Researchers are now able to better understand this complex, devastating and incurable genetic disorder affecting the brain. This advance, reported in the May 18 advance of online publication edition of Nature, could lead to major breakthroughs in the effort to develop new treatments for a range of neurological diseases.

Huntington's is an inherited disease caused by a defective gene that triggers certain nerve cells in the brain to die. Symptoms may include uncontrolled movements, mood swings, cognitive decline, balance problems, and eventually losing the ability to walk, talk or swallow. It affects five to 10 people in every 100,000. There is no known treatment to halt progression of the disease, only medications to relieve symptoms. Death typically occurs 15 to 20 years after onset.

This study marks the first time that researchers have developed a rhesus macaque model of a specific human disease using transgenic technologies, a marked improvement over mouse models. Transgenic animals are created using a recombinant DNA method to modify a genome.

"This research allows scientists to advance beyond mouse models which do not replicate all of the changes in the brain and behavior that humans with Huntington's disease experience," said John D. Harding, Ph.D., director of primate resources at the NIH's National Center for Research Resources (NCRR), which funded the study. "Primate models better mirror human diseases and are a critical link between research with small laboratory animals and studies involving humans."

To unravel the genetic components of this disease, NIH-supported researchers Anthony W.S. Chan, D.V.M., Ph.D.; Xiao-Jiang Li, M.D., Ph.D.; and Shi-Hua Li, M.D., Ph.D., collaborated with their colleagues at the Yerkes National Primate Research Center and other components of Emory University in Atlanta. The research was supported by the NCRR and the National Institute of Neurological Disorders and Stroke (NINDS) at NIH.

The Emory research team developed this transgenic monkey model by introducing altered forms of the Huntington gene into monkey eggs using a viral vector. The eggs were fertilized and the resulting embryos were introduced into surrogate mothers, resulting in five live births. The investigators are now studying the onset of the disease and its behavioral and cognitive effects, with the goal of using the monkey model to better understand disease mechanisms and to design therapies.

Chan, an assistant research professor at the Yerkes Research Center and an assistant professor in the Department of Human Genetics, and his research team produced the HD transgenic rhesus macaques by:

Injecting130 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;

Fertilizing the oocytes by intracytoplasmic sperm injection (ICSI); and

  • Transferring 30 embryos into eight surrogates.
  • This resulted in six pregnancies and five live births (two sets of twins and one singleton); all carried the mutant htt and GFP genes. Two continue to survive.

"Genetic advances make it easy to identify who has inherited the disease gene," said Walter Koroshetz, M.D., deputy director of the NINDS. "Now, with a primate model of Huntington's disease, we are one large step closer to finding better treatments for people with the disease as well as those destined to develop it."

The Yerkes primate center where this advance was made is one of eight supported by NCRR. The centers provide leadership, training and resources to foster scientific discovery and compassionate, quality animal care. Last year, the eight centers located around the country supported more than 2,000 researchers studying a wide range of diseases using non human primate models.

"Yerkes primate center is an ideal place to carry out this work because of its expertise in nonhuman primate transgenesis, non-invasive neural imaging, and experience with behavior assessment," said Dr. Harding.


Story Source:

The above story is based on materials provided by NIH/National Center for Research Resources. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Center for Research Resources. "First Transgenic Monkey Model Of Huntington's Disease Developed." ScienceDaily. ScienceDaily, 19 May 2008. <www.sciencedaily.com/releases/2008/05/080518152643.htm>.
NIH/National Center for Research Resources. (2008, May 19). First Transgenic Monkey Model Of Huntington's Disease Developed. ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2008/05/080518152643.htm
NIH/National Center for Research Resources. "First Transgenic Monkey Model Of Huntington's Disease Developed." ScienceDaily. www.sciencedaily.com/releases/2008/05/080518152643.htm (accessed April 18, 2014).

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