Nav: Home

A new genetic tool to modify and understand gene function

May 22, 2019

Scientists of the National Center for Cardiovascular Research (CNIC) led by Rui Benedito have developed a new genetic tool (iSuRe-Cre) that provides certainty in Cre-inducible genetic modifications, a key technique for understanding gene function.

Most analysis of gene function in biomedical research relies on the use of Cre-lox technology. Since its introduction in 1994, this technology has revolutionized biomedical science because it allows scientists to eliminate or activate the function of any gene in any cell type in the mouse. Using this technology, it has been possible to investigate the precise role of almost any mouse gene, in any cell type, and at a defined time-point, all of which are crucial requirements for understanding the function of genes during organ development, physiology, and disease.

Cre-Lox technology allows the regulation of gene expression at any time or in any cell type thanks to the ability of the Cre recombinase protein to recognize and recombine lox sites introduced at specific locations in the mouse genome, leading to the deletion of the genes being studied.

Despite the major impact of Cre-loxP technology on biomedical research, numerous studies have demonstrated the need for caution in its use. The main problem is that often the Cre activity level is insufficient to fully recombine and eliminate expression of the target gene, generating uncertainty about whether the desired genetic modification has been achieved.

Because the Cre-loxP recombination event is invisible, genetic and fluorescent reporters have been developed to track Cre activity, so that cells reaching a certain threshold of Cre activity are labeled. These reporters have become established as essential genetic tools for monitoring any conditional genetic study. However, as study author Macarena Fernández-Chacón points out, many studies have shown that Cre-induced reporter expression can occur even though other genes with loxP sites are not completely eliminated.

To overcome this technical hurdle, the CNIC team have developed an innovative method based on a new allele called iSuRe-Cre. iSuRe-Cre is compatible with all existing Cre/CreERT2/lox alleles and guarantees high Cre activity in the cells that express the fluorescent reporter. This ultimately increases the efficiency and reliability of the analysis of Cre-dependent gene function. Moreover, the use of the new iSuRe-Cre mice permits the induction of multiple genetic deletions in the same cell. This important property allows the study of functional genetic interactions or epistasis, or in other words, how the function of one or more genes depends on the function of another.

Macarena Fernández-Chacón says that "the use of this new genetic tool will significantly change research projects that depend on the Cre-lox system, because now we can see and be confident about the location of cells that have one or more genes eliminated." Lead investigator Rui Benedito adds that the new genetic tool will be of great interest in biomedical research "because it significantly increases the ease, efficiency, and reliability of genetic modification in the mouse, the most widely used animal model in research." The new study is published in Nature Communications.
-end-
About the CNIC

The Centro Nacional de Investigaciones Cardiovasculares (CNIC), directed by Dr. Valentín Fuster, is dedicated to cardiovascular research and the translation of knowledge gained into real benefits for patients. The CNIC, recognized by the Spanish government as a Severo Ochoa center of excellence, is financed through a pioneering public-private partnership between the government (through the Carlos III Institute of Health) and the Pro-CNIC Foundation, which brings together 12 of the most important Spanish private companies.

Centro Nacional de Investigaciones Cardiovasculares Carlos III (F.S.P.)

Related Genes Articles:

How status sticks to genes
Life at the bottom of the social ladder may have long-term health effects that even upward mobility can't undo, according to new research in monkeys.
Symphony of genes
One of the most exciting discoveries in genome research was that the last common ancestor of all multicellular animals already possessed an extremely complex genome.
New genes out of nothing
One key question in evolutionary biology is how novel genes arise and develop.
Good genes
A team of scientists from NAU, Arizona State University, the University of Groningen in the Netherlands, the Center for Coastal Studies in Massachusetts and nine other institutions worldwide to study potential cancer suppression mechanisms in cetaceans, the mammalian group that includes whales, dolphins and porpoises.
How lifestyle affects our genes
In the past decade, knowledge of how lifestyle affects our genes, a research field called epigenetics, has grown exponentially.
Genes that regulate how much we dream
Sleep is known to allow animals to re-energize themselves and consolidate memories.
The genes are not to blame
Individualized dietary recommendations based on genetic information are currently a popular trend.
Timing is everything, to our genes
Salk scientists discover critical gene activity follows a biological clock, affecting diseases of the brain and body.
New genes on 'deteriorating' Y chromosome
Decoding Y chromosomes is difficult even with latest sequencing technologies.
Newly revealed autism-related genes include genes involved in cancer
Researchers in Italy have applied a computational technique that accounts for how genes interact, to find new networks of related genes that may be involved in autism spectrum disorder.
More Genes News and Genes Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Clint Smith
The killing of George Floyd by a police officer has sparked massive protests nationwide. This hour, writer and scholar Clint Smith reflects on this moment, through conversation, letters, and poetry.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Nina
Producer Tracie Hunte stumbled into a duet between Nina Simone and the sounds of protest outside her apartment. Then she discovered a performance by Nina on April 7, 1968 - three days after the assassination of Dr. Martin Luther King Jr. Tracie talks about what Nina's music, born during another time when our country was facing questions that seemed to have no answer, meant then and why it still resonates today.  Listen to Nina's brother, Samuel Waymon, talk about that April 7th concert here.