Navigation Links
Animal model sheds light on rare genetic disorder, signaling pathway
Date:7/20/2011

SALT LAKE CITY A team of researchers from the University of Utah and Brigham Young University has developed a mouse model of focal dermal hypoplasia, a rare human birth defect that causes serious skin abnormalities and other medical problems. This animal model not only provides insight into studying the cause of focal dermal hypoplasia (FDH), but also offers a novel way to study a signaling pathway that is crucial for embryonic development.

The findings were published July 19, 2011, online in the Proceedings of the National Academy of Sciences.

FDH is an uncommon X chromosome-linked genetic disorder characterized by distinctive skin abnormalities and a wide variety of defects affecting the eyes, teeth, fingernails, skeleton, and other body systems. The exact prevalence of FDH is not known, but about 90 percent of cases occur in females. The disorder has been associated with at least 24 different mutations in a gene called PORCN located on the X chromosome. Based on studies in cultured cells and in lower model organisms, PORCN is known to promote secretion of Wnt signaling proteins, key regulators of embryonic development.

"In addition to the integral role it plays in the development of nearly all body tissues, the Wnt signaling pathway has also been implicated in the development of diseases such as cancer and diabetes," says L. Charles Murtaugh, Ph.D., associate professor of human genetics at the University of Utah and lead author on the study. "In our research, we mutated the mouse version of the PORCN gene to better understand its exact functions in the Wnt signaling pathway."

Murtaugh and his colleagues found evidence that PORCN is required for secretion and activity of Wnt proteins, supporting the widely held hypothesis that FDH is a disease of impaired Wnt signaling. They also found PORCN is essential for formation of the mesoderm, the layer of embryonic cells that gives rise to the connective tissues of the body, as well as the linings of several body cavities and the protective layers of most of the internal organs.

Human geneticists have observed that FDH can be passed from mothers to daughters but not sons.

"Females with FDH have two X-chromosomes, one normal and one mutant. Males only have one X-chromosome, and our work suggests that if they get the mutant chromosome, they would die at very early embryonic stages due to a lack of mesoderm," Murtaugh says. "Females survive to birth, because of their normal copy of the PORCN gene, and present with the disease when born. This is true in our mice as well, as we observed that female mice with mutant PORCN displayed skin and limb abnormalities, which varied widely in severity and closely resembled human FDH."

The hallmark of human FDH is thin or absent patches of the inner layer of the skin, or dermis, which develops from mesodermal cells immediately underneath the embryonic skin, or ectoderm. When Murtaugh and his colleagues selectively deleted PORCN from the ectoderm, they found abnormal development of the underlying dermis, suggesting that ectoderm cells require PORCN to send Wnt signals that promote dermis development.

Along with defects of the dermis, human FDH is commonly associated with defects in the hair, teeth, and nails. Murtaugh and his colleagues found evidence that these and other defects also reflect the function of PORCN in the ectoderm.

"Our development of a PORCN mutant in the mouse gives us a unique genetic tool for studying the precise roles of PORCN in the Wnt signaling pathway and in specific body tissues," says Murtaugh. "In addition to giving us an animal model to study FDH, this PORCN mutant will also be useful for studying cancer and other aspects of development biology that involve Wnt signaling."


'/>"/>

Contact: Phil Sahm
phil.sahm@hsc.utah.edu
801-581-2517
University of Utah Health Sciences
Source:Eurekalert

Related biology news :

1. Loss of top animal predators has massive ecological effects
2. The Animal Connection -- a new perspective on what makes us human
3. The loudest animal is recorded for the first time
4. Ancient symbiosis between animals and bacteria discovered
5. Genome editing, a next step in genetic therapy, corrects hemophilia in animals
6. Why animals dont have infrared vision
7. New type of MRSA in hospitalized patients probably of animal origin
8. Study finds greenhouse gas reduction strategy may be safe for soil animals
9. Blueberrys effects on cholesterol examined in lab animal study
10. Egg cartons not accurate in reporting animal welfare claims
11. UF research aims to help preserve plants, animals caught between forest fragments
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/4/2017)... a global clinical research organization (CRO), announces the launch of Shadow, ... 2017. Shadow is designed to assist medical writers and biometrics teams ... European Medicines Agency (EMA) in meeting the requirements for de-identifying clinical ... ... Tom ...
(Date:6/30/2017)... Today, American Trucking Associations announced Seeing ... and eye tracking software, became the newest member ... "Artificial intelligence and advanced sensing algorithms ... driver,s attentiveness levels while on the road.  Drivers ... fatigue and prevent potential accidents, which could lead ...
(Date:5/16/2017)...  Veratad Technologies, LLC ( www.veratad.com ), an innovative ... verification solutions, announced today they will participate as a ... thru May 17, 2017, in Washington D.C.,s ... Identity impacts the lives of billions ... evolving digital world, defining identity is critical to nearly ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... ... Rosalind™, the first-ever genomics analysis platform specifically designed for life science researchers ... honor of pioneering researcher Rosalind Franklin, who made a major contribution to ...
(Date:10/11/2017)... , ... October 11, 2017 , ... ComplianceOnline’s Medical Device ... on 7th and 8th June 2018 in San Francisco, CA. The Summit brings together ... as several distinguished CEOs, board directors and government officials from around the world to ...
(Date:10/11/2017)... Georgia (PRWEB) , ... October 11, 2017 , ... Disappearing ... taking the lives of over 5.5 million people each year. Especially those living in ... greenovative startup Treepex - based in one of the most pollution-affected countries globally - ...
(Date:10/10/2017)... CA (PRWEB) , ... October ... ... a development-stage cancer-focused pharmaceutical company advancing targeted antibody-drug conjugate (ADC) therapeutics, today ... of targeted HPLN (Hybrid Polymerized Liposomal Nanoparticle), a technology developed in collaboration ...
Breaking Biology Technology: