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Nuclear transfer to pinpoint diseases
This potentially explains why only 1 percent of the 500,000 U.S. Parkinson’s cases and 6.3 million worldwide are considered inherited, according to the National Institutes of Health’s National Institute of Neurological Disorders and Stroke. Hinkle doesn’t know why she developed the disease. “No one in my family had it, and I didn’t know anyone with it. I come from a long line of healthy people.”
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| Dr. Joanne Wojcieszek (left) says that Linda Hinkle is a textbook case of non-inherited Parkinson’s disease. Eighty-five percent of these cases are diagnosed in people at about age 60. Photo Credit: Tom Campbell |
One tool that aids Purdue researchers in their quest to explain such sporadic disease is called “nuclear transfer.” This technique allows scientists to make the earliest stage of an embryo—a zygote—in the laboratory. Nuclear transfer is how the cloned sheep Dolly was produced in a Scottish lab in 1996.
Nuclear transfer involves removing the chromosomes from an animal’s egg and then fusing the “enucleated egg” to a cell from the same type of animal. Machaty, Krisher and Cabot use pig eggs for this process. The donor cell, which replaces the egg’s DNA-carrying nucleus, carries new DNA, the blueprint that will produce desired traits. Producing livestock this way can create animals such as pigs with less fat or sheep with more wool. Nuclear transfer also has opened an important research avenue—the possibility of producing animals that can serve as research models to investigate human and animal diseases.
“Nuclear transfer is a tool for production agriculture as well as for biomedical research models,” Cabot says. “Using that technique, scientists can learn a lot of the basic information we need to answer many questions about disease by making pigs that demonstrate human disease, called ‘models,’ or pigs that have improved production traits.”
Animal models to study disease
Animal models can facilitate researchers’ probes into why the biochemical malfunctions of genes, and proteins they manufacture, cause Parkinson’s, diabetes, infertility and a myriad of other disorders. Currently, most animal models for diseases are mice, rats, Drosophila (fruit fly), C. elegans (a tiny, almost-microscopic worm) and even zebra fish.
Machaty and Purdue College of Pharmacy researcher Chris Rochet say that the points at which proteins abnormally connect with other molecules can cause disease. “Proteins interacting with each other cause biochemical reactions that tell cells how to behave,” Machaty says. “They can determine whether a brain cell—a neuron—will live or die.”
Protein interaction is one area that Rochet studies in his research, which focuses on neurological and muscular disorders. In Parkinson’s, which is one of those illnesses, something causes cells that manufacture a chemical messenger called “dopamine” to die. Dopamine, which affects brain processes that control movement, is manufactured in a part of the brain called the “substantia nigra.”
Rochet uses neurons from mice, rats and human patients for his research in lab dishes. He also collaborates with scientists who use mice and rat models to investigate Parkinson’s and other degenerative neuromuscular diseases.
Although mice and rat models that have defective genes linked to Parkinson’s are available, none fully exhibit the disease. Because of that deficiency, a model closer to human physiology would help advance Parkinson’s research, Rochet says. “There is speculation that the rodent dopamine-producing substantia nigra system is somewhat different from that in people,” Rochet says. “Pig models might be a good compromise. I’m excited about that possibility.”
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