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Mice unable to synthesize vitamin C should become valuable research tool, scientists say

University of North Carolina at Chapel Hill scientists have successfully developed the world's first mice incapable of synthesizing vitamin C, a nutrient essential for growth and healthy bones, teeth, gums, ligaments and blood vessels. The genetically engineered research mice should become a valuable tool in determining vitamin C's role in health and illness, the scientists say.

Dr. Nobuyo Maeda, professor of pathology and laboratory medicine at the UNC-CH School of Medicine, and her colleagues have previously generated mutant mice that showed high cholesterol and atherosclerotic lesions like those found in humans. Such mice now are used widely in research laboratories throughout the world.

"By inactivating a gene that is a key enzyme in ascorbic acid synthesis, we have generated mice that, like humans, depend on dietary vitamin C," Maeda said. "If they don't receive supplementary ascorbic acid, which is another name for vitamin C, within five weeks they become anemic, begin to lose weight and die."

As levels of vitamin C in the mice's blood drop, small but significant increases in their total cholesterol can be measured along with decreases in high-density lipoproteins, the so-called "good cholesterol," she said. But the most striking effects of insufficient vitamin C in the mice are abnormal changes in the wall of the aorta, the main artery channeling blood from the heart to the body.

"Marginal vitamin C deficiency affects the vascular integrity of mice unable to synthesize ascorbic acid, with potentially profound effects on their susceptibility to vascular diseases," Maeda said.

A current, controversial theory about important common illnesses affecting many people such as heart disease and cancer is that oxidative stress may be an important risk factor for disease development, said Dr. Oliver Smithies, Excellence professor of pathology and laboratory medicine at UNC-CH and Maeda's colleague. That is the basis f
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Contact: David Williamson
david_williamson@unc.edu
919-962-8596
University of North Carolina at Chapel Hill
15-May-2000


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