Featured Research

from universities, journals, and other organizations

Solving The Mystery Of The Dancer Mice, And Cleft Lip Too

Date:
April 30, 2004
Source:
University Of Rochester Medical Center
Summary:
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.

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.


Story Source:

The above story is based on materials provided by University Of Rochester Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Rochester Medical Center. "Solving The Mystery Of The Dancer Mice, And Cleft Lip Too." ScienceDaily. ScienceDaily, 30 April 2004. <www.sciencedaily.com/releases/2004/04/040430053652.htm>.
University Of Rochester Medical Center. (2004, April 30). Solving The Mystery Of The Dancer Mice, And Cleft Lip Too. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2004/04/040430053652.htm
University Of Rochester Medical Center. "Solving The Mystery Of The Dancer Mice, And Cleft Lip Too." ScienceDaily. www.sciencedaily.com/releases/2004/04/040430053652.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
'Cadaver Dog' Sniffs out Human Remains

'Cadaver Dog' Sniffs out Human Remains

AP (Oct. 21, 2014) Where's a body buried? Buster's nose can often tell you. He's a cadaver dog, specially trained to find human remains and increasingly being used by law enforcement and accepted in courts. These dogs are helping solve even decades-old mysteries. (Oct. 21) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins