Featured Research

from universities, journals, and other organizations

Scientists revolutionize creation of genetically altered mice to model human disease

Date:
May 2, 2013
Source:
Whitehead Institute for Biomedical Research
Summary:
Scientists have efficiently created mouse models with multiple gene mutations in a matter of weeks. Because the method does not require embryonic stem cells, the approach also could allow any animal to become a model organism.

Using the CRISPR/Cas technique, scientists in the lab of Whitehead Institute Founding Member Rudolf Jaenisch created mice with multiple, precise genetic mutations in a matter of weeks. The conventional method for creating such mice would take several years and thousands of dollars. As this cartoon of the new technique shows, the desired mutations, in this case oligos of Tet1 and Tet2, are microinjected into a very early mouse embryo (zygote), along with Cas9 mRNA and single-guide RNAs (sgRNAs) targeting Tet1 and Tet2. The blastocyst derived from the injected zygote is implanted into a foster mouse, where it grows into a mouse with both Tet1 and Tet2 genes altered.
Credit: Image courtesy of Whitehead Institute for Biomedical Research

Whitehead Institute Founding Member Rudolf Jaenisch, who helped transform the study of genetics by creating the first transgenic mouse in 1974, is again revolutionizing how genetically altered animal models are created and perhaps even redefining what species may serve as models.

Related Articles


"This new method is a game changer," says Jaenisch, who is also a professor of biology at MIT. "We can now make a mouse with five mutations in just three to four weeks, whereas the conventional way would take three to four years. And it's rather straightforward, probably even easier than the conventional way."

Scientists create models in mice by altering specific genes that have been associated with a given disease. The models allow for the study of the development and course of the disease and the effects of various interventions, including genetic and chemical. For the past 20 years, the creation of such models has remained relatively unchanged: scientists insert a piece of DNA into a mouse embryonic stem (ES) cell, inject the modified cell into a very early-stage embryo, called a blastocyst, then implant this developing ball of cells into a foster female mouse. The whole process can take years and tens of thousands of dollars to establish a mouse strain with, for example, a single copy of a gene "knocked out." Such knockouts can only be created in very few species, including mice and rats, whose ES cells can be grown and modified reliably.

The new approach used by scientists in Jaenisch's lab bypasses ES cells to quickly and efficiently produce mice with mutations in both copies of multiple genes. In next week's issue of the journal Cell, Haoyi Wang, Hui Yang, and Chikdu Shivalila describe their technique, which is based on a system that certain bacteria use to fend off viral attacks.

This is the first time that the system, known as CRISPR (for "clustered regularly interspaced short palindromic repeat")/Cas (for "CRISPR-associated"), has been used to alter multiple genes in a single multicellular organism. Shivalila says the process is so accessible that he expects other labs to adopt it quickly.

"For any institution or university with a core facility, we think this will be the way they will start making mice carrying specific mutations because it's a lot faster and so efficient," says Shivalila, one of Jaenisch's graduate students. "We were surprised that we could get two genes 'knocked out' at four loci very, very efficiently, about 80% efficiency. If we used TALENs, a more recent and complicated development in genetic engineering, we got 30% efficiency for just one gene."

Because the CRISPR/Cas technique can generate mutant mice even without using ES cells, a limitation of the conventional method for making models, genetic research may no longer be confined to a limited list of model organisms -- those for which ES cells exist.

"This breaks down the definition of model organism," says Wang, a postdoctoral researcher in Jaenisch's lab. "So now, even with limited resources, any animal with established embryo manipulation procedures could be the subject of genome engineering. With many of the animals' genomes that have been sequenced, we could use this technology to establish efficient genetic manipulations in more species, to study the unique biology of each, and to learn more about evolution."

Thus, Wang, Yang, and Shivalila have used CRISPR/Cas to create mouse models only, but the team is excited broaden its application to other animals.

"We also need to see if the CRISPR/Cas system has any unexpected, undesired off-target effects, changes to the genome that we don't want," says Yang, a postdoctoral researcher in the Jaenisch lab. "So we need study this further to establish the fidelity of the system. But I think this will be the way to go."

This research was supported by Damon Runyon Cancer Research Foundation, Croucher Foundation, National Institutes of Health (NIH) grants R37-HD045022 and R01-CA084198. Jaenisch is an adviser to Stemgent and a cofounder of Fate Therapeutics.


Story Source:

The above story is based on materials provided by Whitehead Institute for Biomedical Research. The original article was written by Nicole Giese Rura. Note: Materials may be edited for content and length.


Journal Reference:

  1. Haoyi Wang, Hui Yang, ChikduS. Shivalila, MeeladM. Dawlaty, AlbertW. Cheng, Feng Zhang, Rudolf Jaenisch. One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering. Cell, 2013; DOI: 10.1016/j.cell.2013.04.025

Cite This Page:

Whitehead Institute for Biomedical Research. "Scientists revolutionize creation of genetically altered mice to model human disease." ScienceDaily. ScienceDaily, 2 May 2013. <www.sciencedaily.com/releases/2013/05/130502131716.htm>.
Whitehead Institute for Biomedical Research. (2013, May 2). Scientists revolutionize creation of genetically altered mice to model human disease. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2013/05/130502131716.htm
Whitehead Institute for Biomedical Research. "Scientists revolutionize creation of genetically altered mice to model human disease." ScienceDaily. www.sciencedaily.com/releases/2013/05/130502131716.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Christmas Kissing Good for Health

Christmas Kissing Good for Health

Reuters - Innovations Video Online (Dec. 22, 2014) Scientists in Amsterdam say couples transfer tens of millions of microbes when they kiss, encouraging healthy exposure to bacteria. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Brain-Dwelling Tapeworm Reveals Genetic Secrets

Brain-Dwelling Tapeworm Reveals Genetic Secrets

Reuters - Innovations Video Online (Dec. 22, 2014) Cambridge scientists have unravelled the genetic code of a rare tapeworm that lived inside a patient's brain for at least four year. Researchers hope it will present new opportunities to diagnose and treat this invasive parasite. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Reuters - Innovations Video Online (Dec. 21, 2014) A team of scientists led by Danish chemist Jorn Christensen says they have isolated two chemical compounds within an existing antipsychotic medication that could be used to help a range of failing antibiotics work against killer bacterial infections, such as Tuberculosis. Jim Drury went to meet him. Video provided by Reuters
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