Featured Research

from universities, journals, and other organizations

And The Beat Goes On: New Insight Into The Genetics Of Congenital Heart Disease

Date:
September 17, 2003
Source:
Cold Spring Harbor Laboratory
Summary:
Using a sophisticated approach to alter gene activity in the embryo, scientists have identified a potential culprit for one of the most common human congenital heart malformations, AVCD (atrioventricular canal defect).

Using a sophisticated approach to alter gene activity in the embryo, scientists have identified a potential culprit for one of the most common human congenital heart malformations, AVCD (atrioventricular canal defect). As Dr. Kai Jiao and colleagues report in the October 1 issue of Genes & Development, proper expression of a single gene, called Bmp4, is essential for normal mouse embryonic heart development – even a 50% reduction leads to AVCD-like defects.

In its most severe form, AVCD is characterized by a large hole in the wall (the septum) that partitions the heart into upper and lower chambers (atria and ventricles, respectively). This defect disrupts the unidirectional flow of blood through the heart, allowing oxygen-rich blood traveling through the left chambers to re-enter the right chambers. The mixture of oxygenated and deoxygenated blood in the right chambers increases the overall volume of blood that the right ventricle must pump to the lungs. This increased blood volume taxes both the heart and lungs, causing heart enlargement, high blood pressure, and, eventually, pulmonary blood vessel damage (i.e. lung disease).

Dr. Jiao and colleagues now show that the reduced expression of Bmp4 may underlie AVCD.

Dr. Hogan, the senior author, now at Duke Medical Center, says: "We quessed that Bmp4 was critical for heart development more than 10 years ago because it is expressed there at high levels. But the gene is also needed by the embryo very early, before the heart has formed. Dr. Jiao hit on the idea of knocking the Bmp4 gene out just in the embryonic heart muscle (cardiomyocytes), leaving it intact everywhere else. What is more, he manipulated the system, using 'conditional tissue specific gene inactivation', so that Bmp4 activity could be titered down to different levels."

Dr. Jaio observed a direct correlation between the level of Bmp4 activity and the ability of the septum to correctly partition the upper and lower heart chambers – what the researchers call "atrioventricular septation": the less Bmp4 present in cardiomyocytes, the more severe the septation defect.

By varying the level of Bmp4 expression, Dr. Jiao and colleagues were able to recapitulate the entire spectrum of defects seen in AVCD patients. They found relatively mild septation deformities in mice whose cardiomyocytes had slightly less-than-normal levels of Bmp4, while mice whose cardiomyocytes were completely devoid of Bmp4 displayed severe AVCD --making these mice useful models for AVCD research.

The researchers note that mice with Bmp4-deficient cardiomyocytes are, in fact, the first and only genetic model with AVCD as its primary defect.

Since AVCD is a common feature of Down syndrome, these mice will also be useful to study the cardiac defects associated with Down syndrome – perhaps even more so than existing Down syndrome models. While the classic animal model of Down syndrome (Trisomy 16 mice) does effectively portray many aspects of this disease, it does not wholly recapitulate the range of cardiac defects seen in Down syndrome patients. Mice with Bmp4-deficient cardiomyocytes do.

Dr. Hogan observes, "Knocking down genes specifically in some heart cells and not in others, and at different times, is becoming an increasingly important tool. Dr Jiao, as well as scientists here at Duke Medical Center, are using this approach to alter the levels of other genes besides Bmp4. As the big picture emerges it may reveal new insights into congenital heart malformations and perhaps ways to treat or prevent them."

Dr Kai Jiao continues his investigations at Vanderbilt University Medical Center.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Cite This Page:

Cold Spring Harbor Laboratory. "And The Beat Goes On: New Insight Into The Genetics Of Congenital Heart Disease." ScienceDaily. ScienceDaily, 17 September 2003. <www.sciencedaily.com/releases/2003/09/030917072441.htm>.
Cold Spring Harbor Laboratory. (2003, September 17). And The Beat Goes On: New Insight Into The Genetics Of Congenital Heart Disease. ScienceDaily. Retrieved August 30, 2014 from www.sciencedaily.com/releases/2003/09/030917072441.htm
Cold Spring Harbor Laboratory. "And The Beat Goes On: New Insight Into The Genetics Of Congenital Heart Disease." ScienceDaily. www.sciencedaily.com/releases/2003/09/030917072441.htm (accessed August 30, 2014).

Share This




More Health & Medicine News

Saturday, August 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

3 Things To Know About The Ebola Outbreak's Progression

3 Things To Know About The Ebola Outbreak's Progression

Newsy (Aug. 29, 2014) Here are three things you need to know about the deadly Ebola outbreak's progression this week. Video provided by Newsy
Powered by NewsLook.com
Killer Amoeba Found in Louisiana Water System

Killer Amoeba Found in Louisiana Water System

AP (Aug. 28, 2014) State health officials say testing has confirmed the presence of a killer amoeba in a water system serving three St. John the Baptist Parish towns. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Who Could Be Burnt by WHO's E-Cigs Move?

Who Could Be Burnt by WHO's E-Cigs Move?

Reuters - Business Video Online (Aug. 28, 2014) The World Health Organisation has called for the regulation of electronic cigarettes as both tobacco and medical products. Ciara Lee looks at the impact of the move on the tobacco industry. Video provided by Reuters
Powered by NewsLook.com
CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

Newsy (Aug. 28, 2014) CDC director Tom Frieden says the Ebola outbreak is even worse than he feared. But he also said there's still hope to contain it. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins