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Solving the mystery of the dancer mice, and cleft lip too

By watching mice "dance" and comparing the DNA of the dancers to their flat-footed siblings, scientists have discovered a genetic cause of cleft lip and palate in mice, a finding that is already being used to search for a similar genetic defect in humans.

A team led by Rulang Jiang of the Center for Oral Biology at the University of Rochester Medical Center found that a gene known as Tbx10 is responsible for causing cleft lip and palate in mice. The group, which reported its results April 26 in the on-line edition of the Proceedings of the National Academy of Sciences, is now working with a group at the University of Iowa to find a similar mutation in humans.

The Rochester team studied mice that naturally carry a genetic mutation called Dancer, so named because mice with one copy of the Dancer mutation twist as they walk, toss their heads abnormally, and have balance problems due to inner-ear damage caused by the mutation. For more than 35 years it's been known that these mice are also more susceptible than normal mice to being born with cleft lip and palate, while mice with two copies of the mutation are always born with the defect.

To narrow down the stretch of DNA where the genetic defect resides, graduate student Jeffrey Bush bred many litters of mice and monitored the offspring for head-tossing and other Dancer signs. Through meticulous analysis of the genetics of the dancers vs. the non-dancers, Bush, Jiang, and Research Professor Yu Lan narrowed down the location of the gene to a small area on chromosome 19. Instead of having to pick through all of a mouse's estimated 25,000 genes to find Dancer, the team had to contend with a region containing only 97 genes.

"It's like the difference between looking for a small town using a map of the entire United States vs. a map just of New York State," says Bush, a graduate student in the Department of Biology. "Once we were able to narrow down the location of the mutation, the job bec
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Contact: Tom Rickey
trickey@admin.rochester.edu
585-275-7954
University of Rochester Medical Center
30-Apr-2004


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