Researchers at Northwestern are screening tens of thousands of mice to identify gene mutations that cause sex reversal, after receiving a $2.8 million grant from the National Institutes of Health.
Sex reversal occurs when individuals possess the chromosomes of one sex but display the physical attributes of the other.
Investigators use a technique called genomewide mutagenesis to identify mutations in the mouse genome that are passed on to future generations.
So far, scientists have focused on the presence or absence of the male-determining factor located on the Y chromosome.
They also are looking at another gene believed to play an important role in reproductive gland development and infertility.
“We hope to understand the way in which gonadal determination occurs and what genes are involved in determining that,” said Jeffrey Weiss, a research associate professor at the Feinberg School of Medicine.
Researchers developed the mouse model based on experience with gene mutations in humans.
The findings will be applied to human cases, Weiss said.
In mice, genetically programmed events cause the gonads to develop into either testes or ovaries about 10.5 days into the 21-day gestation period, Weiss said. Scientists describe this as a “battle of the sexes” in which genes compete to determine gonadal development.
More than 600 mice have been screened since September.
The mutagenesis is conducted at the Neurogenomics Center on the Evanston Campus.
“It’s a good time to be doing genetics,” Weiss said. “There is a lot of information going online to make it easier.”
Feinberg Prof. J. Larry Jameson, the study’s principal investigator, said the team expects that milder forms of mutations may cause infertility. About 70 percent of male infertility cases stem from unknown causes, he said.
Psychology Prof. Michael Bailey, who studies human sexuality, will be awaiting the developments.
“I do not know if this research has implications for my own, but understanding the biology of sex determination and reversal is utterly fascinating and obviously important to the intellectually curious,” Bailey wrote in an e-mail.
The study is modeled after the pioneering research of neurobiology and physiology Prof. Joseph Takahashi, who discovered the first circadian rhythm gene in mammals, the mouse gene “Clock.”
The five-year study is one of four projects funded by the National Institute of Child Health and Human Development to find mutations that lead to developmental problems and infertility.
Researchers conducting these studies hail from NU, Sloan Kettering Institute for Cancer Research, Baylor College of Medicine, and Harvard Medical School’s Brigham and Women’s Hospital.
