PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

CRISPR/Cas genome engineering system generates valuable conditional mouse models

2013-08-29
(Press-News.org) CAMBRIDGE, Mass. (August 29, 2013) – Whitehead Institute researchers have used the gene regulation system CRISPR/Cas to engineer mouse genomes containing reporter and conditional alleles in one step. Animals containing such sophisticated engineered alleles can now be made in a matter of weeks rather than years and could be used to model diseases and study gene function.

"We've used CRISPR/Cas to mutate genes before, but the nature of the targeted mutations has been unpredictable," says Whitehead Founding Member Rudolf Jaenisch. "Now we can make specific deletions defined by two cuts. We can use this to make conditional mice in one step, and we can easily and very efficiently insert pieces of DNA up to three thousand base pairs It used to be much more work to make such mice."

The CRISPR/Cas (for "clustered regularly interspaced short palindromic repeat/CRISPR-associated) system is based on an immune defense against viral invaders in bacteria and archaea. Scientists recently have adapted that defense to alter the genomes of mouse and human cells quickly and efficiently. Until now, however, researchers had yet to use CRISPR/Cas to create one of the most useful tools for genetic research: the conditional mutant mouse.

A conditional mutant mouse's genome contains a gene or collection of genes that can be turned on or off using a particular signal. By turning the genes on or off, scientists can tease apart the role of certain genes in biological functions and diseases.

Previously, scientists created such model organisms using a complex and time-consuming process that requires using embryonic stem cells (ESCs). Unfortunately, scientists have only been able to efficiently manipulate the ESCs of mice and rats, a restriction that has hobbled this type of research.

Using CRISPR/Cas, Jaenisch and his lab have created mice with conditional alleles, as well as mice that carry multiple tagged genes that report whether these genes are being expressed. Their work is described in the September 12 issue of the journal Cell.

The researchers' experiments also allay concerns regarding CRISPR/Cas's off-target activity.

"Recent studies in human cancer cell lines raised some concerns on the specificity of CRISPR/Cas," says Chikdu Shivalila, a co-author of the Cell paper and a graduate student in the Jaenisch lab, "Our study shows that the non-specific DNA cleavages could happen, but they are rare and predictable."

The Jaenisch lab's latest work opens up a number of avenues for future research.

"The methods we described in this work will greatly accelerate the speed of generating gene modified animals," says Hui Yang, a postdoctoral researcher in the Jaenisch lab and co-author. "I'd like to use CRISPR/Cas to establish sophisticate disease models using this method."

Because CRISPR/Cas does not rely on ESCs, it can be used to genetically modify any animal, including livestock.

"We haven't tried it yet, but I'd like to adapt the CRISPR/Cas system for genome engineering in large animals, such as primate for disease modeling, or cattle for agricultural purposes," says Haoyi Wang, a co-author and a postdoctoral researcher in the Jaenisch lab. "If so, this method could be very important economically, too."

###

This work is supported the Croucher Foundation and National Institutes of Health (NIH) grants HD 045022 and R37CA08419.

Written by Nicole Giese Rura

Rudolf Jaenisch's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology at Massachusetts Institute of Technology.

Full Citation:

"One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas mediated genome engineering"

Cell, September 12, 2013.

Hui Yang (1,4), Haoyi Wang (1,4), Chikdu S. Shivalila (1,2,4), Albert W. Cheng (1,3), Linyu Shi (1), Rudolf Jaenisch (1,3).

1. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
2. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
3. Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
4. These authors contributed equally to this work.

END



ELSE PRESS RELEASES FROM THIS DATE:

Pre-pregnancy hormone testing may indicate gestational diabetes risk

2013-08-29
OAKLAND, Calif., August 29, 2013 — Overweight women with low levels of the hormone adiponectin prior to pregnancy are nearly seven times more likely to develop gestational diabetes, according to a Kaiser Permanente study published today in the journal Diabetes Care. Adiponectin protects against insulin resistance, inflammation and heart disease. Using Kaiser Permanente HealthConnect®, an electronic health records system, the researchers retrospectively identified about 4,000 women who gave voluntary blood samples between 1985 and 1996 during routine care and subsequently ...

Digesting milk in Ethiopia: A case of multiple genetic adaptations

2013-08-29
A genetic phenomenon that allows for the selection of multiple genetic mutations that all lead to a similar outcome -- for instance the ability to digest milk -- has been characterised for the first time in humans. The phenomenon, known as a 'soft selective sweep', was described in the population of Ethiopia and reveals that individuals from the Eastern African population have adapted to be able to digest milk, but via different mutations in their genetic material. A team of geneticists from UCL, University of Addis Ababa and Roskilde University have shown that five ...

Human heart disease recently found in chimpanzees

2013-08-29
Los Angeles -- While in the past century there have been several documented examples of young, healthy athletes who have died suddenly of heart disease during competitive sporting events, a new study finds that this problem also extends to chimpanzees. According to an article published today in the SAGE journal Veterinary Pathology, Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), a human heart disease that causes sudden cardiac death in teenagers and young adults (particularly healthy athletes), has now been identified in chimpanzees. "It is the first description ...

Learning how the brain takes out its trash may help decode neurological diseases

2013-08-29
ANN ARBOR—Imagine that garbage haulers don't exist. Slowly, the trash accumulates in our offices, our homes, it clogs the streets and damages our cars, causes illness and renders normal life impossible. Garbage in the brain, in the form of dead cells, must also be removed before it accumulates, because it can cause both rare and common neurological diseases, such as Parkinson's. Now, University of Michigan researchers are a leap closer to decoding the critical process of how the brain clears dead cells, said Haoxing Xu, associate professor in the U-M Department of Molecular, ...

New PRA gene identified in Phalenes and Papillons

2013-08-29
Professor Hannes Lohi's research group at the University of Helsinki and Folkhälsan Research Center, Finland, has identified a mutation in CNGB1 gene, causing progressive retinal atrophy (PRA) in the Phalene and Papillon dog breeds. PRA is one of the most common causes of blindness in dogs and in human. CNGB1 mutations have been previously associated with the corresponding human disease, human retinitis pigmentosa. This study highlights the shared genetic etiology of many canine and human genetic disorders, and provides new tools to investigate PRA mechanisms while the ...

More efficient production of biofuels from waste with the help of modified yeasts

2013-08-29
A significant portion of the petroleum consumed by the transport sector must be replaced in the long term by renewable energy. Therefore, it is of the utmost economic and ecological importance to optimise the production of biofuels from renewable raw materials. Researchers from VIB who are associated with KU Leuven have developed yeast strains that produce bio-ethanol from waste with an unprecedented efficiency. As a result, they are well placed to become important players on a global scale in this burgeoning industry. Johan Thevelein (VIB/KU Leuven): "Our new yeast strains ...

Customer satisfaction increases the value and interest of company shares for institutional investors

2013-08-29
How do institutional investors react to customer satisfaction with companies on the stock market? A research group run by Jaakko Aspara, who is a professor in the Department of Marketing at Aalto University School of Business in Finland, conducted a study showing that improved customer satisfaction with a company causes institutional investors to increase their ownership in that firm and has a positive impact on share value. The study was published in the highly regarded Journal of the Academy of Marketing Science. It shows that transient institutional investors, such ...

Echolocation

2013-08-29
Biologists at LMU have demonstrated that people can acquire the capacity for echolocation, although it does take time and work. As blind people can testify, we humans can hear more than one might think. The blind learn to navigate using as guides the echoes of sounds they themselves make. This enables them to sense the locations of walls and corners, for instance: by tapping the ground with a stick or making clicking sounds with the tongue, and analyzing the echoes reflected from nearby surfaces, a blind person can map the relative positions of objects in the vicinity. ...

Unexpected use of former cancer drug

2013-08-29
Researchers at Lund University have unexpectedly discovered that an old cancer drug can be used to prevent rejection of transplanted tissue. The researchers now have high hopes that their discovery could lead to new treatments for both transplant patients and patients with autoimmune diseases. The researchers behind the study, which has been published in the scientific journal PLOS ONE, work at the Rausing Laboratory, Lund University, where they have conducted research on brain tumours over many years. "Our group were studying the effects of the old tumour drug Zebularine, ...

Where can coral reefs relocate to escape the heat?

2013-08-29
Fossil fuel emissions are impacting corals through high temperatures which can cause their deaths and ocean acidification which makes it difficult for them to produce their skeletons. In a study published today in Global Change Biology, Dr Elena Couce, Professor Andy Ridgwell and Dr Erica Hendy used computer models to predict future shifts in the global distribution of coral reef ecosystems under these two stressors. The researchers found that warming impacts were dominant, with a significant decline in suitability for corals near the equator. Dr Couce said: "Just ...

LAST 30 PRESS RELEASES:

Signs identified that precede sudden arrhythmic death syndrome in young people

Discovery of bacteria's defence against viruses becomes a piece of the puzzle against resistance

Pre-eclampsia is associated with earlier onset and higher incidence of cardiovascular risk factors

Warwick astronomers discover doomed pair of spiralling stars on our cosmic doorstep

Soil conditions significantly increase rainfall in world’s megastorm hotspots

NK cells complexed with bispecific antibody yield high response rates in patients with lymphoma

Planetary health diet and mediterranean diet associated with similar survival and sustainability benefits

Singapore launches national standard to validate antimicrobial disinfectant products

Molecular stool test could improve detection of tuberculosis in adults with HIV

Suspected fibrocartilaginous embolus in Asian small-clawed otter (Aonyx cinereus)

Enhancing heat transfer using the turbulent flow of viscoelastic fluids

Exercise as an anti-ageing intervention to avoid detrimental impact of mental fatigue

UMass Amherst Nursing Professor Emerita honored as ‘Living Legend’

New guidelines aim to improve cystic fibrosis screening

Picky eaters by day, buffet by night: Butterfly, moth diets sync to plant aromas

Pennington Biomedical’s Dr. Leanne Redman honored with the E. V. McCollum Award from the American Society for Nutrition

CCNY physicists uncover electronic interactions mediated via spin waves

Researchers’ 3D-printing formula may transform future of foam

Nurture more important than nature for robotic hand

Drug-delivering aptamers target leukemia stem cells for one-two knockout punch

New study finds that over 95% of sponsored influencer posts on Twitter were not disclosed

New sea grant report helps great lakes fish farmers navigate aquaculture regulations

Strain “trick” improves perovskite solar cells’ efficiency

How GPS helps older drivers stay on the roads

Estrogen and progesterone stimulate the body to make opioids

Dancing with the cells – how acoustically levitating a diamond led to a breakthrough in biotech automation

Machine learning helps construct an evolutionary timeline of bacteria

Cellular regulator of mRNA vaccine revealed... offering new therapeutic options

Animal behavioral diversity at risk in the face of declining biodiversity

Finding their way: GPS ignites independence in older adult drivers

[Press-News.org] CRISPR/Cas genome engineering system generates valuable conditional mouse models