 |
|
Gene involved in common birth defect also regulates skin biology
October 16, 2006Following up on an earlier discovery that a gene called IRF6 is involved in the common birth defect cleft lip and palate, researchers at the University of Iowa Roy J. and Lucille A. Carver College of Medicine and their colleagues have identified the function of the gene. Their latest findings, published online Oct. 15 in Nature Genetics, reveal an unexpected role for IRF6 in the growth and development of skin cells, a discovery that may have implications for wound healing and cancer research.
In 2002, Brian Schutte, Ph.D., UI associate professor of pediatrics and nursing, and Jeff Murray, M.D., UI professor of pediatrics, pediatric dentistry and biological sciences, and the Roy J. Carver Chair in Perinatal Health, led a study showing that mutations in IRF6 cause Van der Woude syndrome (VWS), a rare, dominantly inherited form of cleft lip and palate. Subsequently, the researchers found that this gene also is mutated in 10 to 15 percent of the more common, so-called non-syndromic cases of cleft lip and palate. Cleft lip and palate, where the lip or both the lip and palate (roof of the mouth) fail to close, occurs in approximately one of every 1,000 babies.
In order to determine the function of this gene, the researchers created mice that lacked IRF6. These mice had very abnormal skin as well as a cleft palate. Detailed analysis of the mice revealed that IRF6 regulates the proliferation and differentiation of keratinocytes - the main cell type in the epidermis or outer layer of skin. Keratinocytes also provide a protective barrier around the mouth, gut, liver, lung, kidney and other internal organs.
"This study really looks at the role of IRF6 in skin development. By focusing on skin we felt we could learn more about this specific cell type that is also abnormal in the palate," Schutte said. "The insight we gained into the function of IRF6 will help focus research efforts to identify other genes involved in cleft lip and palate."
Skin is an extremely important tissue, as it is the largest tissue in the body and it provides a critical external barrier. Normal epidermis has four layers of keratinocytes. The UI study showed that mice that lack IRF6 have abnormal skin development and are missing the upper two cellular layers of the epidermis. The researchers also showed abnormal proliferation of keratinocytes in one of the remaining two layers and failure of these cells to die off or differentiate as normal.
Although humans with Van der Woude syndrome do not have skin defects, a similar human condition, called popliteal ptyergium syndrome (PPS) that is also caused by mutations in IRF6, does cause skin abnormalities in addition to cleft lip and palate. Thus, the UI researchers were not completely surprised by the skin abnormalities in the mice.
Mice provided a particularly good animal model for the UI study because mice and humans have very similar facial development and both share the distinctive mammalian structure of a palate, which separates the nasal airway from the mouth allowing a baby to suckle. In addition, it is fairly easy to create mutations in mice to study a particular gene's function.
"Having an animal model for a major human birth defect like cleft lip and palate provides us with the opportunity to investigate ways to better treat and prevent these disorders much more quickly than was previously possible," Murray said. "Dr. Schutte's work has also expanded our knowledge of other critical areas of human health such as the role of our skin in development and in how wounds and scars may heal."
"Our results open many new avenues of research because the function we discovered for IRF6 is vastly different than the best understood function for the other IRF genes," Schutte added.
IRF6 belongs to a family of nine IRF genes, which have been extensively investigated. The UI study reveals that IRF6 has a different function than the other known IRF genes, which are all primarily involved in the immune response. Its newly identified role in cell proliferation and differentiation may mean that IRF6 also is involved in other medically important areas of biology such as cancer and wound healing.
The main funding for the study is from a National Institute of Dental and Craniofacial Research grant for the UI Craniofacial Anomalies Research Center (CARC). Murray is the principal investigator for the grant. The CARC also supported a complementary study by researchers at the University of Manchester in England, who are collaborating with Schutte and Murray. The Manchester team investigated a different mutation in the mouse IRF6 gene and observed similar results to the UI study. This second study will also be published in Nature Genetics.
"The support from the CARC was critical to the completion of these two studies because several different disciplines were needed to characterize the abnormalities of the mice," Schutte said. "The CARC brought together specialists to attack the problem from many different directions."
University of Iowa
"This study really looks at the role of IRF6 in skin development. By focusing on skin we felt we could learn more about this specific cell type that is also abnormal in the palate," Schutte said. "The insight we gained into the function of IRF6 will help focus research efforts to identify other genes involved in cleft lip and palate."
Skin is an extremely important tissue, as it is the largest tissue in the body and it provides a critical external barrier. Normal epidermis has four layers of keratinocytes. The UI study showed that mice that lack IRF6 have abnormal skin development and are missing the upper two cellular layers of the epidermis. The researchers also showed abnormal proliferation of keratinocytes in one of the remaining two layers and failure of these cells to die off or differentiate as normal.
Although humans with Van der Woude syndrome do not have skin defects, a similar human condition, called popliteal ptyergium syndrome (PPS) that is also caused by mutations in IRF6, does cause skin abnormalities in addition to cleft lip and palate. Thus, the UI researchers were not completely surprised by the skin abnormalities in the mice.
Mice provided a particularly good animal model for the UI study because mice and humans have very similar facial development and both share the distinctive mammalian structure of a palate, which separates the nasal airway from the mouth allowing a baby to suckle. In addition, it is fairly easy to create mutations in mice to study a particular gene's function.
"Having an animal model for a major human birth defect like cleft lip and palate provides us with the opportunity to investigate ways to better treat and prevent these disorders much more quickly than was previously possible," Murray said. "Dr. Schutte's work has also expanded our knowledge of other critical areas of human health such as the role of our skin in development and in how wounds and scars may heal."
"Our results open many new avenues of research because the function we discovered for IRF6 is vastly different than the best understood function for the other IRF genes," Schutte added.
IRF6 belongs to a family of nine IRF genes, which have been extensively investigated. The UI study reveals that IRF6 has a different function than the other known IRF genes, which are all primarily involved in the immune response. Its newly identified role in cell proliferation and differentiation may mean that IRF6 also is involved in other medically important areas of biology such as cancer and wound healing.
The main funding for the study is from a National Institute of Dental and Craniofacial Research grant for the UI Craniofacial Anomalies Research Center (CARC). Murray is the principal investigator for the grant. The CARC also supported a complementary study by researchers at the University of Manchester in England, who are collaborating with Schutte and Murray. The Manchester team investigated a different mutation in the mouse IRF6 gene and observed similar results to the UI study. This second study will also be published in Nature Genetics.
"The support from the CARC was critical to the completion of these two studies because several different disciplines were needed to characterize the abnormalities of the mice," Schutte said. "The CARC brought together specialists to attack the problem from many different directions."
University of Iowa
Birth Defect Current Events and Birth Defect News RSSLocal health investigation sheds light on gastroschisis birth defect
Results of an investigation conducted by University of Nevada, Reno researchers, public health officials and area physicians published this week in the Archives of Pediatrics & Adolescent Medicine, indicate that Washoe County experienced a cluster of a particular birth defect, gastroschisis, during the period April 2007 - April 2008.
Secrets of the 4 chambers revealed by reptile hearts
The first genetic link in the evolution of the heart from three-chambered to four-chambered has been found, illuminating part of the puzzle of how birds and mammals became warm-blooded.
Unlikely genetic suspect implicated in common brain defect
A genetic search that wound its way from patients to mouse models and back to patients has uncovered an unlikely gene critically involved in a common birth defect which causes mental retardation, motor delays and sometimes autism, providing a new mechanism and potentially improving treatment for the disorder.
Scientists identify gene vital to early embryonic cells forming a normal heart and skull
New research from Cincinnati Children's Hospital Medical Center highlights the critical role a certain gene and its protein play during early embryonic development on formation of a normal heart and skull.
Embryology Study Offers Clues to Birth Defects
Gregg Duester, Ph.D., professor of developmental biology at Burnham Institute for Medical Research (Burnham), along with Xianling Zhao, Ph.D., and colleagues, have clarified the role that retinoic acid plays in limb development.
Hypospadias, a birth defect of the male urethra, is not increasing in New York state
In recent decades, there have been periodic reports of a worldwide decline in sperm count and quality.
Treatment for extreme nausea, vomiting during pregnancy
Nausea and vomiting are telltale indicators of pregnancy, affecting more than 80 percent of future mothers. For a few moms-to-be, symptoms can become so severe that hospitalization is required.
Time of conception linked to birth defects in United States
A study published in the April 2009 issue of the medical journal Acta Pædiatrica is the first to report that birth defect rates in the United States were highest for women conceiving in the spring and summer. The researchers also found that this period of increase risk correlated with increased levels of pesticides in surface water across the United States.
'Suspending asthma treatment a bad option for expectant mothers': Study
Pregnant women suffering from asthma run a greater risk of giving birth prematurely if they suspend their asthma treatments. According to a Université de Montréal study, published in Respiratory Medicine, the probability of suffering from hypertension during pregnancy also increases for women who interrupt their asthma treatment.
New study finds increased prevalence of left-handedness in children with facial development disorder
A new study by physician researchers from Hasbro Children's Hospital and Children's Hospital Boston has identified an increased prevalence in left-handedness in children with a congenital disorder known as hemifacial microsomia (HFM).
More Birth Defect Current Events and Birth Defect News Articles
 |
Before We Are Born: Essentials of Embryology and Birth Defects With STUDENT CONSULT Online Access (Before We Are Born: Essentials of Embryology & Birth Defects) by Keith L. Moore BA MSc PhD FIAC FRSM (Author), T. V. N. Persaud MD PhD DSc FRC Path(Lond) (Author) Zero in on the most essential concepts in human embryology and development! Concise and richly illustrated, this popular book delivers the embryology knowledge you need in a highly efficient, reader-friendly format. The comprehensively updated 7th edition comes with access to the complete contents online via Student Consult, plus 18 phenomenal embryology animations, additional review questions and answers, and more Editor Keith L. Moore, BA, MSc, PhD, FIAC, FRSM is the recipient of the first (2007) "Henry Gray/Elsevier Distinguished Educator Award"-the American Association of Anatomists' highest award for excellence in human anatomy education at the medical/dental, graduate, and undergraduate level of teaching-a testament to his masterful teaching abilities, which help make this... |
|
Abdc News by Assn of Birth Defect Children ABDC News is the quarterly publication of the Association of Birth Defect Children. It provides news, a listing of resources and networks, family profiles, and a wide range of articles designed to assist parents and caretakers of children with disabilities. | |
 |
Diseases and Disorders - Birth Defects by Barbara Sheen (Author) Every 3.5 minutes, a baby in the United States is born with a birth defect. This interesting and informative book uses plentiful primary and secondary sources to give insights into different birth defects, their diagnosis and treatment, and the challenges of living with them. It provides prospective parents with preventive steps, which may help ensure the health of their babies. Readers are given a window into the future through a discussion of stem cell and gene therapy research. (20051001) |
 |
Carol Bond's Folic Acid 800 Mcg (Part of the Vitamin B Family, Considered a Brain Food, and Needed for Energy Production Also Taken Before, During and After Pregnancy Can Help Prevent Birth Defects) 250 Tablets by Carol Bond Health Foods Considered a brain food, folic acid is needed for energy production and the formation of red blood cells. It also strengthens immunity by aiding in the proper formation and functioning of white blood cells. Applications include: Alcoholism, anemia, arteriosclerosis, baldness, diarrhea, depression, mental illness, mental retardation, immune system, birth-defect prevention, fatigue, ulcers, stress, blood disorders. Scientific Data: Various studies support the use of folic acid nutritional supplements during and after pregnancy to prevent birth defects and post-partum depression. Note: A tongue that is red and sore may indicate a folic acid deficiency Applications: Alcoholism, anemia, arteriosclerosis, baldness, diarrhea, depression, mental illness, mental retardation, immune system,... |
 |
Birth Defects Awareness Ribbon Mouse Pad by MyHeritageWear.com The Birth Defects Ribbon proudly displayed on a mouse pad. There is no better way to achieve awareness for the meaning of the Birth Defects Ribbon than to display it on your mouse pad for everyone to see. The mouse pad measures at 9.25 x 7.75, it is machine washable, and the colors will not fade or run. Start gaining awareness today by presenting your Birth Defects Ribbon mouse pad at work or at home. It is certain to keep your mouse rolling in style all while gaining support and awareness! |
|
Smile Starring: Sean Astin, Beau Bridges, Linda Hamilton, Erik Von Detten, Song Jia Also With: Edward J. Pei (Cinematographer), Neil Giraldo (Composer) | |
 |
Young Girl W. Arms Deformed from a Thalidomide Induced Birth Defect Photographic Poster Print, 12x16 by Art.com Young Girl W. Arms Deformed from a Thalidomide Induced Birth Defect is digitally printed on archival photographic paper resulting in vivid, pure color and exceptional detail that is suitable for any museum or gallery display. Finding that perfect piece to match your interest and style is easy and within your budget! |
 |
Perfect Birth Defect One Nature (Primary Contributor) |
 |
Home Starring: David Duchovny, Gillian Anderson Also With: FOX (Producer) |
 |
Chemically Induced Birth Defects by James Schardein (Author) WIL Research Laboratories, Inc., Ashland, OH. This volume's purpose is to catalog the available data on drugs and chemicals with respect to their potential teratogenicity in animals and humans. Extensive references. Expanded-outline format. Graphs and charts throughout. For medical students, researchers, and clinicians. |
| © 2009 BrightSurf.com |