Mutant Gene Linked to Miscarriages in Mouse Study by Dr. Edward Schmidt of MSU

Researchers studying mice say they have identified a gene that appears
critical in preventing miscarriages.

By Jacqueline Stenson Reuters

Doctors have long been perplexed by the fact that in a normal pregnancy the mother’s immune system
does not launch a full-blown attack against the fetus, viewing it as a foreign invader because it has
dissimilar genetic material that comes from the father.

The new study offers a potential explanation. The findings indicate that the TBP gene (for TATA binding
protein) is important in enabling the placenta to protect the fetus from the mother’s immune system, said
study author Dr. Edward Schmidt, an assistant professor of veterinary molecular biology at Montana State
University in Bozeman.

Normally, placentas know how to "hide" from the mother’s immune system, Schmidt told Reuters Health.
But when female mice were bred to have dysfunctional versions of the TBP gene, most of the pregnancies
ended in miscarriage, Schmidt and colleagues report in the July 12th issue of Cell.

The mutant gene produces a defective protein that interferes with the ability of the placenta to escape
detection by the mother’s immune system, Schmidt said. As a result, the mother’s immune system
attacks and destroys the fetus in most cases, he explained. "It’s not that the mother is hyper-responsive,
it’s that the placenta is failing to ‘hide,"’ he said.

Adding further support to this idea, when the researchers studied mutant mice that had severely weakened
immune systems, the pregnancies were normal.

"These findings show that there’s a very complex interaction between the placenta of the developing
fetus…and the mother’s immune system," Schmidt said.

The next step, he added, is to gain a better understanding of this process and to determine if this gene is
involved in some of the many unexplained miscarriages in women.

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