Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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 became easier."

Bush and colleagues did some homework on those 97 genes and discovered that one of the genes is Tbx10; that caught their interest, Bush says, because it encodes one of a family of proteins known to be crucial in development by turning on and off other genes. Two closely related genes are known to play a role in cranio-facial development, he says, and mutations in other "T-box" genes result in birth defects.

Looking more closely, the team found the precise genetic defect responsible for the Dancer mice: They discovered a chunk of genetic material from another gene – a specialized strip of DNA responsible for turning a gene on – embedded into the DNA of the Tbx10 gene. They found that in mice with the Dancer mutation, the Tbx10 gene is active in places it’s normally not, including the developing face.

While the team is investigating exactly how Tbx10 contributes to cleft lip and palate, Jiang suspects there are at least 10 genes linked to the disorder. Previously a gene in mice was linked to some cases of cleft palate, and then scientists found a similar gene in humans – but still the cause of most cases of cleft lip and palate in humans is not known.

"It’s likely that mutations in many different genes could cause clefting," says Jiang. "Now that we’ve identified one specific mutation, we will investigate the molecular networks that control facial development to look for other important players in the clefting process."

Going from a few cells of an embryo to a full-fledged face – whether human or mouse – requires the cooperation of hundreds of genes turning on or off at just the right time, Jiang says.

"The face develops initially from five separate parts surrounding the oral cavity – hundreds of genes are involved in bringing the parts together to form the intact face. The development of the face has been under-studied in biology. It’s a complex problem," says Jiang, an assistant professor of Biomedical Genetics whose work is supported by the National Institute of Dental and Craniofacial Research.

Worldwide about 1 of every 700 people is born with a cleft lip, either with or without a cleft palate. Asians and American Indians are slightly more likely to have the birth defect than Caucasians, while African Americans have a much lower risk. The disfiguring gap or opening in the lip or the roof of the mouth can cause dental and speech problems, trouble eating, and other difficulties. In the United States the problem is usually corrected through multiple surgeries over the course of many years.

"Facial clefts are a significant and disfiguring birth defect," says Jiang. "A baby born with clefting might need years of multiple surgeries. It also creates a social burden for the person."

For tens of thousands of children around the world, the problem has been fixed by volunteers for Operation Smile, a non-profit organization that provides facial reconstruction surgery for indigent children and young adults in the United States and 20 developing countries. Strong pediatrician Chin-To Fong has traveled to the Philippines as part of Operation Smile teams and is now faculty adviser to a medical student chapter of the group. This Sunday, May 2, at 10 a.m., students in the School of Medicine & Dentistry are holding a 5K run in Genesee Valley Park as a fundraiser for Operation Smile.

Tom Rickey | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences

nachricht Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>