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 Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>