Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mutation in Mouse Circulatory Gene That Mimics A Form of Congenital Heart Disease

08.06.2005



Mutations in a critical gene that controls heart and blood vessel development in mouse embryos mimics a type of congenital heart disease in humans, according to new research led by Michael S. Parmacek, MD, Director of the Penn Cardiovascular Institute at the University of Pennsylvania School of Medicine. Congenital heart disease (CHD) occurs in approximately one in one hundred newborn infants. Knowing the basic genetic causes of congenital heart disease will allow for the development of CHD prenatal diagnosis, as well as treatments to prevent or correct infant and adult heart disease.

Using genetically engineered mice, the researchers found that mice with a mutation in the gene for myocardin-related transcription factor B (MRTF-B) had defects in developing arteries associated with the embryonic heart. Specifically, these mice had a variation of a childhood condition known as a truncus arteriosis defect, a relatively rare form of CHD that occurs in infants in which the aorta does not appropriately separate from the pulmonary artery. (Click on thumbnail above to view full-size image). As a result, oxygenated and deoxygenated blood mix, resulting in insufficient amounts of oxygen being transported to tissues. This causes cyanosis, which is commonly referred to as “blue babies.” Senior author Parmacek and his colleagues published their findings in this week’s early online edition of the Proceedings of the National Academy of Sciences.

Using the gene itself as a marker, the researchers confirmed that the problems in the mouse blood vessels originated from defects in the cardiac neural crest cells, stem cells that migrate from regions of the brain to the heart in developing embryos. These cells populate the heart and eventually differentiate into the smooth muscle cells of the major blood vessels.



“When we looked at the embryonic heart and great arteries during early development in the mice, we saw a variety of defects in the major arteries, suggesting defective patterning of the newly formed blood vessels, including the pulmonary artery, the carotid artery, and the aorta,” notes Parmacek. “These were all consistent with the defects observed later on that caused the embryos not to survive after birth.”

Overall, the researchers demonstrated that the cardiac neural crest cells that originate in the brain do migrate to the heart and outflow tract areas; but, unlike in normal mice, the cells with mutations did not differentiate into smooth muscle cells. As a result, the cells did not form the structure that separates the aorta from the pulmonary artery. “This is the first evidence that a block in stem-cell differentiation is responsible for forms of congenital heart disease,” says Parmacek. “Understanding how MRTF-B works will let us see how this critical junction in the development of the circulatory system regulates how tissues unfold downstream.”

The study was funded in part by the National Institutes of Health. Penn study co-authors are Jian Li, Xiaohong Zhu, Mary Chen, Lan Cheng, Deying Zhou, MinMin Lu, Kevin Du, and Jonathan A. Epstein.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

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

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>