Copper Counts

Copper could be more important to the health of your unborn baby than folic acid, giving up smoking or abstaining from alcohol — according to a new study at the University of Michigan Medical School.

In the June 5 issue of the Proceedings of the National Academy of Sciences, U-M scientists report that copper and a protein called Ctr1, which helps copper get inside cells, are essential for normal embryonic development in mice. Although scientists knew that Ctr1 was involved in copper transport in yeast microorganisms, no one knew exactly how the gene worked in mammals until now.

"Since the genetic structure and function of Ctr1 is nearly identical in mice and humans, it is very likely that Ctr1 is essential for human embryonic development, as well," says Dennis J. Thiele, Ph.D., a professor of biological chemistry in the U-M Medical School, who directed the study.

"Without copper," Thiele says, "cells can't produce energy, metabolize iron or detoxify free radicals. Without copper, we can't grow blood vessels, synthesize neuropeptides that control muscle contractions, or make the collagen that gives our skin its elasticity."

Thiele's research team created a new strain of mice by using genetic engineering technology to remove one of two alleles — or copies of the Ctr1 gene — found in normal mice. Although these heterozygous mice appeared and acted normal, U-M researchers found that their brains and spleens contained about half as much copper as was found in normal littermates.

The big surprise came when researchers bred male and female heterozygous mice to see what would happen to mice without either copy of the Ctr1 gene. When Thiele examined mouse embryos from these crosses, he discovered that embryos without the Ctr1 gene all died 10 to 12 days after fertilization. In addition, all these embryos were much smaller than normal and had major abnormalities in organ and cell development.

"I anticipated the importance of copper in development, but I didn't expect it to be so critical that all the mouse embryos without Ctr1 would die," Thiele said. "Based on these results, it wouldn't surprise me to find that human embryos lacking both copies of Ctr1 are aborted spontaneously during pregnancy."

To test whether copper supplements would help, U-M researchers added it to the drinking water of female experimental mice three weeks before and during their pregnancies. Although they received 50 to 100 times more copper than control mice, the effect on their embryos was unchanged.

"These data suggest there is no alternate system for copper uptake into cells that can compensate for loss of the plasma membrane Ctr1 transporter, and that the presence of at least one functional copy of the Ctr1 copper transporter gene is essential for normal embryonic development," Thiele says.

This research was supported by grants from the National Institutes of Health, the International Copper Association and the American Heart Association.

Jaekwon Lee, Ph.D., U-M post-doctoral research fellow, and Joseph R. Prohaska, Ph.D., of the University of Minnesota-Duluth, were co-authors of the study.

-Sally Pobojewski

Read the complete story online at: www.med.umich.edu/opm/newspage/coppermouse.htm

Information on Dennis Thiele's research:
www.med.umich.edu/biochem/all.faculty/thiele.html

For information on copper and health from the International Copper Association, visit:
www.copperinfo.com/health/health_fr.htm