For some time medical researchers have known that pregnant women who are severely deficient in fibrinogen, a protein important for blood clotting, will miscarry 100 percent of the time. What hasn’t been known is why. Until now.
Using mice they had genetically engineered to mimic the human condition, scientists from Notre Dame’s W.M. Keck Center for Transgene Research recently identified the mechanism. Upon examining the embryos of altered mice at various points in their pregnancy, researchers found that the fertilized egg apparently implanted normally. Soon afterward, however, problems developed at the attachment site, where fibrinogen normally would be found. The site was observed to be less stable. In mice lacking the protein, the attachment site would rupture, resulting in intrauterine bleeding.
“Without fibrinogen you have no way to control blood clotting,” says Frank Castellino, director of the Keck Center and dean of Notre Dame’s College of Science. “So the animal bleeds out and spontaneously aborts.”
Keck Center scientists were able to rescue pregnancies of the protein-deficient mice by treating them with fibrinogen. “This study demonstrates the critical role of this blood coagulation protein in maintaining pregnancy,” Castellino says.
The Keck Center uses targeted gene deletion technology to study the genes involved in blood coagulation. “We ‘chip’ out a gene, make our changes and re-insert it in the chromosome, and observe the animal’s development to see the gene’s effect,” Castellino explains. “If you’re doing these experiments in a test tube, you only see what you’re testing for. In the whole animal, you see everything, even unanticipated effects, such as its role in pregnancy maintenance.” Blood clotting genes also have been shown to be involved in atherosclerosis and cancer.
John Monczunski is an associate editor of this magazine.