Navigation Links
Scientists revolutionize the creation of genetically altered mice to model human disease

CAMBRIDGE, Mass. (May 2, 2013) 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.

"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 organismsthose 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."


Contact: Nicole Rura
Whitehead Institute for Biomedical Research

Related medicine news :

1. Scientists Pinpoint Most Major Genes Behind Deadly Blood Cancer
2. Temple scientists weaken HIV infection in immune cells using synthetic agents
3. HIV Cure Looks Promising, Danish Scientists Contend
4. Guelph scientists develop first vaccine to help control autism symptoms
5. Scientists Spot Cancer Metabolism Changes
6. Work By Female Scientists Gets Judged More Harshly: Study
7. Scientists May Have Spotted Brains Numbers Center
8. Scientists scan the human heart to create digital anatomical library
9. Scientists Create Breast Cancer Survival Predictor
10. Molecule treats leukemia by preventing cancer cell repair, Jackson Laboratory scientists report
11. Scientists map elusive 3-D structure of telomerase enzyme, key actor in cancer, aging
Post Your Comments:
(Date:12/1/2015)... ... December 01, 2015 , ... On Tuesday 27 Oct ... to educate the personnel on spinal decompression therapy and offer his professional help. ... procedure. The benefits come from creating negative intradiscal pressure which is conducive to ...
(Date:12/1/2015)... ... December 01, 2015 , ... The Multiple System Atrophy Coalition has announced the ... System Atrophy (MSA) research, timed today to coincide with Giving Tuesday 2015, a global ... their ability to work and be productive, to do simple daily activities like walking ...
(Date:12/1/2015)... ... December 01, 2015 , ... The North American Meat ... that meat and poultry play in a healthy, balanced diet. , includes ... visitors can check their “meat IQ,” a section offering straight talk on controversies, ...
(Date:12/1/2015)... ... December 01, 2015 , ... World Patent Marketing , a vertically ... patent that allows for easier packing and organizing of items into one big, portable ... says Scott Cooper, CEO and Creative Director of World Patent Marketing and Desa ...
(Date:12/1/2015)... ... December 01, 2015 , ... Henderson, a town of about ... Internet through a partnership this year with Aeneas Internet and Telephone. , With ... destination for entrepreneurs who want to build a business. Whether startups or long ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... -- A large study of patients with breast cancer who ... found no increased risk of recurrence. The Kaiser Permanente ... National Cancer Institute. --> ... drug taken by women with breast cancer to reduce ... for five years, but has notable side effects, including ...
(Date:12/1/2015)... BOTHELL Wash. and VANCOUVER ... Monitoring Committee (DMC) meeting, OncoGenex Pharmaceuticals, Inc. (NASDAQ: ... trial is continuing based on the pre-planned interim futility ... safety review, no new safety issues were identified by ... to all analyses and final results are expected in ...
(Date:12/1/2015)... HERNDON, Va. , Dec. 1, 2015 ... (FDA) Drug Supply Chain Security Act (DSCSA) approaches, ... helping small and independent pharmacies comply with looming ... --> InfiniTrak is entering endorsement agreements with ... a pharmacy services administration organization (PSAO) to exclusively ...
Breaking Medicine Technology: