Geneticist Sally A. Camper, AS ’77, has been working at the University of Michigan for years to discover the sources of inherited biological defects. Thanks to a mouse named Sebastian, her research group hit a genetic jackpot.
By studying a specially bred line of mice with a hyperactive circling behavior, the team recently isolated a gene linked to inherited deafness and discovered a way to ensure that at least some of their offspring have normal hearing and balance.
The method holds potential for application to humans as well, Camper says.
The ability to hear and maintain balance, for both mice and men, depends on tiny hairs in the inner ear called stereocilia, which transmit signals through the nervous system to the brain. "The stereocilia are normally long and sway in response to sound, like a wheatfield in the wind," Camper says.
The family of laboratory mice used for her genetic studies was found to have stereocilia so short, Camper says, "that they look like a mowed field."
Searching for a mutated gene that causes an inherited defect is a needle-in-a-haystack task, but Camper’s group used high-tech, transgenic technology to find the particular gene on the mouse chromosome.
The trial-and-error method involved removing a specific piece of DNA cloned from a normal mouse and inserting it with tiny needles into fertilized deaf-mouse eggs. If the baby mice were all born deaf, then a different segment of DNA was tried.
Ultimately, Camper’s group in the genetic lab at Michigan’s medical school produced a newborn mouse, named Sebastian, with perfect hearing, even though his parents could not hear. Building on that data, scientists at the National Institutes of Health identified a similar gene in humans.
Camper and her associates found the mouse deafness gene almost by accident.
For the past decade, Camper has been working mainly on pituitary gland development and various hormones. "One of the mice I was studying had a pituitary defect, and I was trying to figure out the defective gene," Camper says. "We had done quite a lot of mapping of mouse chromosome 11, and we were involved in a really big effort generating a genetic map of (the pituitary) region of that chromosome. Deafness was one of the mutants nearby."
As it turned out, the team identified three genetic defects near the pituitary one, including deafness, progressive neurological degeneration and a gene for the "vestigial tail," Camper says. The last gene turned out to be related to development of a short mouse tail and serious spinal column defects, such as spina bifida.
Linking mouse deafness to human deafness was just a short jump, scientifically, Camper says.
"We established a link with the National Institutes of Health, which had been studying deafness in an isolated village in Indonesia," says Camper.
"In evolution, genes that are neighbors on a chromosome tend to stay neighbors, so we could use the strengths of the human genome project to get the human deafness gene very quickly. They mapped it to human chromosome 17," Camper says.
Will the success with Sebastian lead to eliminating congenital deafness in people?
"That’s kind of difficult to envision at this time," says Camper. Gene therapy with eggs "involves such strong ethical issues that I don’t think there is any effort right now" to use it with humans.
But, Camper says that engineering newborn mice with the ability to hear could lead to ways of curing mice (and humans) already deaf.
"One of the things we can do with mice is to determine the feasibility of gene therapy, to see if we can replace the [deafness] gene after the mice are born," she says. "If you could restore some hearing function, you could design some kind of rational therapy."
Eventually, she says, doctors may be able to use that therapy to help children who are born deaf.
"It’s an exciting prospect. But, there are a number of challenges. The inner ear is inside a bony structure, and it’s not very accessible for delivery of a missing protein. And, hair cells are difficult to get DNA into," Camper says.
Her deafness research was featured this spring in the journal, Science.
A native of Dover, Del., Camper was a chemistry major at the University, where she also took part in an undergraduate research project with Harold White, professor of chemistry and biochemistry. "At one point, studying egg yolk protein, I found I liked working in the lab and doing things that had a biological link," she says.
She earned her Ph.D. in biochemistry at Michigan State University in 1983, receiving a postdoctoral fellowship from Fox Chase Cancer Center in Philadelphia, where she worked from 1984 to 1988.
Camper recently was honored with a Faculty Recognition Award at the University of Michigan, where she organized a nationally recognized Transgenic Animal Core Facility. More than 1,000 different families of mice with specific genetic defects have been bred at the facility, to help scientists seek cures for some of humankind’s most troubling developmental problems.
Camper and her husband Robert Lyons, also a Michigan State biochemist, have two children, Erik and Liz.
–Phil Milford