Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mouse Model Sheds Light on Rare Genetic Disorder, Signaling Pathway

21.07.2011
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.

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 School of Medicine 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.”

Phil Sahm | EurekAlert!
Further information:
http://www.utah.edu

More articles from Life Sciences:

nachricht First-of-its-kind chemical oscillator offers new level of molecular control
15.12.2017 | University of Texas at Austin

nachricht New technique could make captured carbon more valuable
15.12.2017 | DOE/Idaho National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

New technique could make captured carbon more valuable

15.12.2017 | Life Sciences

First-of-its-kind chemical oscillator offers new level of molecular control

15.12.2017 | Life Sciences

A chip for environmental and health monitoring

15.12.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>