Research team discovers possible genetic mechanism behind congenital heart defects

November 03, 2004

TORONTO (November 3, 2004) -- Researchers at The Hospital for Sick Children (Sick Kids) and Mount Sinai Hospital (MSH) have discovered a possible genetic mechanism behind congenital heart defects. This finding has implications for understanding how congenital heart defects occur, and may lead to genetic tests for certain defects, such as proteins that determine how genes are expressed. This also opens new insights into how general chromosome properties can relate to specific disease processes. This research is reported in the November 4, 2004 issue of the scientific journal Nature.

"It was previously believed that all cells during development contained the same chromatin remodelling proteins that unwind DNA, a process that is important for genes to be turned on. However, we identified one of these proteins, called Baf60c, that is expressed specifically in the developing heart," said Dr. Benoit Bruneau, the study's co-principal investigator, a Sick Kids scientist and an assistant professor of Molecular and Medical Genetics at the University of Toronto (U of T).

"When we completely suppressed the function of the Baf60c protein, there were dramatic cardiovascular defects. When we suppressed just half of the protein, the result was a defect that resembled one seen in infants," added Dr. Bruneau, also Canada Research Chair in Developmental Cardiology and member of U of T's Heart & Stroke/Richard Lewar Centre of Excellence.

Using a novel way of reducing gene function called in vitro RNAi, the team developed mouse models with different levels of the protein. They were then able to see the effects of the suppressed protein using optical projection tomography at the Mouse Imaging Centre at Sick Kids. Knockout mice, where a specific gene is replaced, or removed, allow researchers to have precise control over a specific gene in order to study its function.

"This new protein may provide new diagnostic tools and insights into how to treat cardiovascular problems," said Dr. Janet Rossant, the study's co-principal investigator and a senior investigator at the Samuel Lunenfeld Research Institute at MSH, as well as a professor of Molecular and Medical Genetics at U of T.

Congenital heart defects are among the most prevalent and serious conditions affecting children, occurring in approximately one out of 100 live births in Canada. The next steps for this research involve examining patients with congenital heart defects to see if they, like the mouse model, have this modified protein.

Other members of the research team include the study's co-lead authors Dr. Heiko Lickert of the Samuel Lunenfeld Research Institute at MSH and Dr. Jun Takeuchi of the Sick Kids Research Institute, Dr. Ingo von Both, Dr. Jeffrey Wrana, Dr. Fionnuala McAuliffe and Dr. S. Lee Adamson, all from the Samuel Lunenfeld Research Institute at MSH, and Dr. Mark Henkelman and Dr. Johnathon Walls from Sick Kids.

This research was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario, the March of Dimes Birth Defects Foundation, the National Cancer Institute of Canada, the Canada Foundation for Innovation, the Ontario Innovation Trust, the Ontario Research and Development Challenge Fund, and Sick Kids Foundation.
-end-
The Hospital for Sick Children, affiliated with the University of Toronto, is Canada's most research-intensive hospital and the largest centre dedicated to improving children's health in the country. Its mission is to provide the best in family-centred, compassionate care, to lead in scientific and clinical advancement, and to prepare the next generation of leaders in child health.

Mount Sinai Hospital is recognized nationally and internationally for its excellence in the provision of compassionate patient care, teaching and research. Our key priority programs are Infectious Diseases, Women's and Infants' Health, Cancer Surgery, General Internal and Subspecialty Medicine, Digestive Diseases, Arthritis and Orthopaedics, Emergency Medicine, Primary and Community Health and the Samuel Lunenfeld Research Institute. We are a University of Toronto affiliated patient care, teaching and research centre.

University of Toronto

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.