Fast track to mouse modeling

Fewer laboratory animals for basic medical research

2013-04-02

(Press-News.org) Scientists use genetically modified laboratory mice to investigate the underlying mechanisms of diseases. These "knockout" mice carry genes or gene regions that are thought to trigger diseases.

For laboratories, the knockout technique requires a lot of time and effort. "Scientists start by engineering a genetic defect into embryonic stem cells," explains Prof. Wolfgang Wurst, who carries out research at Technische Universität München (TUM) and Helmholtz Zentrum München. "Then they implant the manipulated stem cells into a mouse embryo."

Genetic defects made to order

After multiple steps, organisms are created which have both modified and unmodified cells. The mice have to be crossed several times until offspring are produced which carry the knockout characteristic in all of their body cells. Including all tests, it takes scientists between one and two years to produce a functioning mouse model.

But now the team led by Prof. Wurst and Dr. Ralf Kühn have developed a new method, allowing them to complete the process in a much shorter time – just a little over four months. They modified the genes directly in the fertilized mouse egg cells so that all the cells in the bodies of the offspring would have the same genetic defect. "By eliminating the time-consuming crossing stage, laboratories will be able to produce mouse models much quicker and with much fewer test animals," remarks Wurst.

High-precision cutting of DNA strands

The team used TALEN enzymes(*) for its research experiments. These DNA tools have a dual function: One part recognizes and binds to a particular gene, while another cuts the DNA strand in situ. These ultra-precise DNA "scalpels" were developed just a few years ago.

"TALEN enzymes have a simple, modular structure," says Wurst. "This means that we can create a number of variants to cut through all genes in the genome and modify them for a specific purpose." The technique will allow scientists to knock out particular genes, introduce genetic defects within cells and repair genetic defects.

"We have used the TALEN process to implant mutations associated with human dementia in mouse germ cells. These animal models will help us understand the molecular mechanisms behind dementia. The advantage of the technique is that we will in principle be able to model all hereditary diseases in the test mice," adds Wurst.

INFORMATION:

(*)TALEN: Transcription activator-like effector nuclease

Publication:

Direct production of mouse disease models by embryo microinjection of TALENs and oligodeoxynucleotides; Benedikt Wefers, Melanie Meyer, Oskar Ortizk Martin Hrabé de Angelis, Jens Hansen, Wolfgang Wurst and Ralf Kühn, PNAS, http://www.pnas.org/content/110/10/3782

Contact:

Prof. Dr. Wolfgang Wurst
Technische Universität München
Chair of Developmental Genetics
Helmholtz Zentrum München (German Research Center for Environmental Health) Institute of Developmental Genetics
T: +49.89.3187-4110
E: wurst@helmholtz-muenchen.de
W: http://www.helmholtz-muenchen.de/en/idg/

ELSE PRESS RELEASES FROM THIS DATE:

Reviewing the work of 1 of the greatest beetle collectors: Napoleon's General Dejean

2013-04-02

Two Canadian scientists have undertaken the challenging task to bring up to date the catalogues written by one of the most passionate collectors of beetles, Coleoptera, in the 19th century, Pierre Dejean. Dr. Yves Bousquet and Dr. Patrice Bouchard, who work with the Canadian National Collection of Insects, Arachnids and Nematodes, have now produced a pioneering detailed review of the important nomenclatural and taxonomic data in these rich publications. Two articles analyzing the Coleoptera genera in the second (1833) and third (1836) catalogues of Dejean's collection were ...

Vitamin P as a potential approach for the treatment of damaged motor neurons

2013-04-02

Biologists from the Ruhr-Universität Bochum have explored how to protect neurons that control movements from dying off. In the journal "Molecular and Cellular Neuroscience" they report that the molecule 7,8-Dihydroxyflavone, also known as vitamin P, ensures the survival of motor neurons in culture. It sends the survival signal on another path than the molecule Brain Derived Neurotrophic Factor (BDNF), which was previously considered a candidate for the treatment of motoneuron diseases or after spinal cord damage. "The Brain Derived Neurotrophic Factor only had a limited ...

Putting larval cobia to the acid test

2013-04-02

MIAMI – April 2, 2013 – Ocean acidification, which occurs as CO2 is absorbed by the world's oceans, is a source of concern for marine scientists worldwide. Studies on coral, mollusks, and other ocean denizens are helping to paint a picture of what the future might entail for specific species, should carbon emissions continue to increase. In a new study published in Global Change Biology, University of Miami (UM) Rosenstiel School of Marine & Atmospheric Science researchers Sean Bignami, Su Sponaugle, and Robert Cowen are the first to study the effects of acidification ...

3-D scaffolds a new tool to fight cancer

2013-04-02

Porous polymer scaffolds fabricated to support the growth of biological tissue for implantation may hold the potential to greatly accelerate the development of cancer therapeutics. Researchers at Rice University and the University of Texas MD Anderson Cancer Center in Houston and Mount Sinai Medical Center in New York reported this week that three-dimensional scaffolds used to culture Ewing's sarcoma cells were effective at mimicking the environment in which such tumors develop. Their research appears online this week in the Proceedings of the National Academy of ...

CAMH study shows mental illness associated with heavy cannabis use

2013-04-02

People with mental illnesses are more than seven times more likely to use cannabis weekly compared to people without a mental illness, according to researchers from the Centre for Addiction and Mental Health (CAMH) who studied U.S. data. Cannabis is the most widely used illicit substance globally, with an estimated 203 million people reporting use. Although research has found links between cannabis use and mental illness, exact numbers and prevalence of problem cannabis use had not been investigated. "We know that people with mental illness consume more cannabis, ...

Switching to a power stroke enables a tiny but important marine crustacean to survive

2013-04-02

Olympic swimmers aren't the only ones who change their strokes to escape competitors. To escape from the jaws and claws of predators in cold, viscous water, marine copepods switch from a wave-like swimming stroke to big power strokes, a behavior that has now been revealed thanks to 3-D high-speed digital holography. Copepods are tiny crustaceans found in nearly every aquatic environment on Earth. By some estimates, they are the most abundant animals on the planet. Their change in stroke in cold water helps them escape a slew of predators, from larval fish to crabs, ...

New insights on how spiral galaxies get their arms

2013-04-02

Spiral galaxies are some of the most beautiful and photogenic residents of the universe. Our own Milky Way is a spiral. Our solar system and Earth reside somewhere near one of its filamentous arms. And nearly 70 percent of the galaxies closest to the Milky Way are spirals. But despite their common shape, how galaxies like ours get and maintain their characteristic arms has proved to be an enduring puzzle in astrophysics. How do the arms of spiral galaxies arise? Do they change or come and go over time? The answers to these and other questions are now coming into focus ...

Disease over-diagnosis can result in needlessly medicating infants

2013-04-02

The American Board of Internal Medicine Foundation recently recommended against routine use of medications to treat infants for gastroesophageal reflux (GERD), commonly known as reflux disease. From 1999-2004 the use of prescription medications to treat this disease in infants increased 700 percent. However, these acid-reducing medications have been found to be ineffective at alleviating symptoms commonly diagnosed as GERD, such as excessive crying and spitting up. This suggests that GERD is often over-diagnosed in infants. In a new study, MU Psychology Professor Laura ...

Stillbirth or pre-term birth outcomes linked to elevated risk of blood clots after pregnancy

2013-04-02

(Washington)- Newly identified pregnancy-related events, such as stillbirth or pre-term birth, may dramatically increase a woman's risk of developing a potentially deadly blood clot immediately after pregnancy, according to the results of a large, population-based study published online today in Blood, the Journal of the American Society of Hematology (ASH). Venous thromboembolism, or VTE, is a clotting disorder that includes both deep-vein thrombosis (DVT) and pulmonary embolism (PE). DVT is a blood clot that typically forms in the deep veins of the leg. It can develop ...

Fighting listeria and other food-borne illnesses with nanobiotechnology

2013-04-02

Troy, N.Y.—Engineering researchers at Rensselaer Polytechnic Institute have developed a new method to kill deadly pathogenic bacteria, including listeria, in food handling and packaging. This innovation represents an alternative to the use of antibiotics or chemical decontamination in food supply systems. Using nature as their inspiration, the researchers successfully attached cell lytic enzymes to food-safe silica nanoparticles, and created a coating with the demonstrated ability to selectively kill listeria—a dangerous foodborne bacteria that causes an estimated 500 ...

NFCR congratulates Dr. Robert C. Bast, Jr. on receiving the AACR-Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research

Fast track to mouse modeling

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: