Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

30.04.2004


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:
http://www.urmc.rochester.edu/

More articles from Life Sciences:

nachricht Monitoring biodiversity with sound: how machines can enrich our knowledge
18.06.2019 | Georg-August-Universität Göttingen

nachricht Uncovering hidden protein structures
18.06.2019 | Universität Konstanz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The hidden structure of the periodic system

The well-known representation of chemical elements is just one example of how objects can be arranged and classified

The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...

Im Focus: Tube anemone has the largest animal mitochondrial genome ever sequenced

Discovery by Brazilian and US researchers could change the classification of two species, which appear more akin to jellyfish than was thought.

The tube anemone Isarachnanthus nocturnus is only 15 cm long but has the largest mitochondrial genome of any animal sequenced to date, with 80,923 base pairs....

Im Focus: Tiny light box opens new doors into the nanoworld

Researchers at Chalmers University of Technology, Sweden, have discovered a completely new way of capturing, amplifying and linking light to matter at the nanolevel. Using a tiny box, built from stacked atomically thin material, they have succeeded in creating a type of feedback loop in which light and matter become one. The discovery, which was recently published in Nature Nanotechnology, opens up new possibilities in the world of nanophotonics.

Photonics is concerned with various means of using light. Fibre-optic communication is an example of photonics, as is the technology behind photodetectors and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

Uncovering hidden protein structures

18.06.2019 | Life Sciences

Monitoring biodiversity with sound: how machines can enrich our knowledge

18.06.2019 | Life Sciences

Schizophrenia: Adolescence is the game-changer

18.06.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>