Featured Research

from universities, journals, and other organizations

Transgenic Mice Created By Researchers May Shed Light On Human Heart Disease

Date:
January 28, 1998
Source:
University Of Colorado At Boulder
Summary:
A University of Colorado at Boulder research team has created several strains of transgenic mice that carry gene mutations for a heart disease that has been shown to be the leading cause of sudden death in young athletes.

A University of Colorado at Boulder research team has created several strains of transgenic mice that carry gene mutations for a heart disease that has been shown to be the leading cause of sudden death in young athletes.

Known as hypertrophic cardiomyopathy, the genetic disease is marked by significant thickening of the heart muscle, said Leslie Leinwand, chair of CU-Boulder's molecular, cellular and developmental biology department who is spearheading the research effort. The disease can obstruct blood flow in heart ventricles, lessening their ability to pump blood into the arteries.

"This is a difficult disease to diagnose," said Leinwand. "While symptoms can include shortness of breath, dizziness and chest pain, often the first sign of the disease is death."

Although the most frequent cause of the disease has been shown to be a mutation on a tiny portion of a single gene that produces the protein myosin, it is not known why the myosin gene causes mortality, she said. "We have created these transgenic mice to help us understand the biological processes and hopefully test new therapeutic agents."

Myosin is a major component of muscle tissue and "molecular motor" that creates the energy and motion to allow heart contractions to occur.

Healthy humans have two copies of the normal gene for myosin while people with the disease have a mutated form, just as the mice do, said Leinwand. To create a transgenic mouse, the researchers added a mutated myosin gene to the genetic material of a normal mouse, which was taken up randomly by one of its chromosomes.

In humans and mice, healthy heart muscle is very organized and densely packed with structural protein that allows it to contract, she said. But in heart muscle carrying the mutant form of the myosin gene, the normal, parallel alignment of muscle cells is lost and the cells appear disorganized.

Although people with hypertrophic cardiomyopathy often have larger hearts than normal people, the hearts of most athletes enlarge normally due to rigorous exercise, making the condition more difficult to detect, she said. The research project is funded primarily by the National Institutes of Health.

The CU-Boulder team also has created a mouse that carries a mutant gene for the protein troponin T, which is related to the sensing process of tiny muscle fibrils located in the heart. Although mutant troponin T genes cause little or no heart enlargement, the production of even small amounts of the protein by mutant genes causes a high incidence of sudden death, she said.

"In troponin mutant mice, we can manipulate how much of the protein they make," she said. "We have found that when the gene makes even a small amount of the protein, it can cause death within eight hours."

The team exercises the transgenic mice on a custom-built treadmill in the department's new, $1.5 million, pathogen-free Center for Mammalian Biology in an effort to measure their heart responses to vigorous exercise. "This kind of research is new to the Boulder campus," said Leinwand, who noted the new tools and techniques now available in mammalian biology play a major role in the application of basic knowledge to human welfare.

Leinwand and her collaborators, who have patented their mutant myosin transgenic mice through the University Technology Corp., recently co-founded a university spin-off company called Myogen to search for new ways of treating hypertrophic cardiomyopathy in humans. "We are looking for ways to improve the motor activity in the heart muscles," she said. "The answer may turn out to be a therapeutic agent."

Leinwand has had preliminary discussions with a major pharmaceutical company to pursue possible therapetic drug screening projects. Leinwand's team includes MCDB research associate Karen Vikstrom, cardiologists Dr. Jil Tardiff and Dr. Setsuya Miyata as well as several graduate students. The current study involves about 1,000 mice.


Story Source:

The above story is based on materials provided by University Of Colorado At Boulder. Note: Materials may be edited for content and length.


Cite This Page:

University Of Colorado At Boulder. "Transgenic Mice Created By Researchers May Shed Light On Human Heart Disease." ScienceDaily. ScienceDaily, 28 January 1998. <www.sciencedaily.com/releases/1998/01/980128074140.htm>.
University Of Colorado At Boulder. (1998, January 28). Transgenic Mice Created By Researchers May Shed Light On Human Heart Disease. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/1998/01/980128074140.htm
University Of Colorado At Boulder. "Transgenic Mice Created By Researchers May Shed Light On Human Heart Disease." ScienceDaily. www.sciencedaily.com/releases/1998/01/980128074140.htm (accessed October 21, 2014).

Share This



More Plants & Animals News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

'Cadaver Dog' Sniffs out Human Remains

'Cadaver Dog' Sniffs out Human Remains

AP (Oct. 21, 2014) Where's a body buried? Buster's nose can often tell you. He's a cadaver dog, specially trained to find human remains and increasingly being used by law enforcement and accepted in courts. These dogs are helping solve even decades-old mysteries. (Oct. 21) Video provided by AP
Powered by NewsLook.com
White Lion Cubs Born in Belgrade Zoo

White Lion Cubs Born in Belgrade Zoo

AFP (Oct. 20, 2014) Two white lion cubs, an extremely rare subspecies of the African lion, were recently born at Belgrade Zoo. They are being bottle fed by zoo keepers after they were rejected by their mother after birth. Duration: 00:42 Video provided by AFP
Powered by NewsLook.com
Traditional Farming Methods Gaining Ground in Mali

Traditional Farming Methods Gaining Ground in Mali

AFP (Oct. 20, 2014) He is leading a one man agricultural revolution in Mali - Oumar Diatabe uses traditional farming methods to get the most out of his land and is teaching others across the country how to do the same. Duration: 01:44 Video provided by AFP
Powered by NewsLook.com
Goliath Spider Will Give You Nightmares

Goliath Spider Will Give You Nightmares

Buzz60 (Oct. 20, 2014) An entomologist stumbled upon a South American Goliath Birdeater. With a name like that, you know it's a terrifying creepy crawler. Sean Dowling (@SeanDowlingTV) has the details. Video provided by Buzz60
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:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

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