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 Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>