Of mice and men: Rat model may advance hemophilia research

When it comes to rats, blood is not always thicker than water.

Yale School of Medicine professor Carmen Jane Booth and her team of researchers have developed a new animal model for hemophilia A, a disease that affects the blood’s ability to clot. Their eventual goal is to improve treatment for humans with the disorder, she said.

“This is the first and only spontaneous rat model of hemophilia A in the world,” Booth said.

The inspiration for the model started with one rat with a giant bruise, Booth said. When many of the rat’s relatives started bruising as well, she assembled a group of researchers to determine why these rats were showing symptoms of hemophilia A. After ruling out environmental factors, the team discovered that the rats had a decreased amount of factor VIII, a protein essential for blood clotting.

“Essentially, one small change in a single protein gave the rats hemophilia A,” Booth said. “When we discovered that, I was like a kid in a candy shop.”

Booth added that the gene mutation in the rats was very close to the gene mutations found in people with severe hemophilia. She and her team found that treating the rats with artificial factor VIII for humans helped relieve many of the symptoms in the rats.

Hemophilia A, which affects the body’s blood clotting response, occurs in around one in every 10,000 human births, Booth said. When unaffected humans get a minor cut, clotting starts in under a minute. But in people with hemophilia A, bleeding does not stop and can lead to anything from bruises to fatal hemorrhaging from everyday activities.

The creation of the animal model could be used in the future to study hemophilia A and its treatment in humans. Subjects for studying hemophilia A in the past included mice, dogs and humans, but mice were often too small and dogs and humans too expensive and ethically dubious to use. However, rats are excellent, said team member Peter Marks, an associate professor at the School of Medicine.

“First, the location of the mutated gene [for hemophilia A] is different than it is in other animals, so both males and females are affected equally,” Marks said. “Rats are also a nice size, large enough to test a pump and other treatment methods that wouldn’t quite work on a mouse.”

Booth said she hopes the study could provide a new model for those studying gene therapy for hemophilia A, or help improve delivery methods for existing treatments.

Their study will be published online in the Journal of Thrombosis and Haemostasis.

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