A&M lab genetically alters mice for cloning research
Published: Monday, October 31, 2011
Updated: Wednesday, July 25, 2012 21:07
Located on the far west corner of campus, a 34,000 square foot facility sits amongst the squawking birds and fenced horses of the University's College of Veterinary Medicine and Biomedical Sciences. However, in this facility, the Texas Institute of Genomic Medicine (TIGM) handles a notably smaller animal — the mouse.
A research institute of Texas A&M's AgriLife Research, TIGM genetically engineers a special kind of mouse — known as a "knockout mouse" — that has identical genes isolated by TIGM. These genes come from a particular genetic strain, known as Black 6, which is the most common generational line for medical and scientific research.
With more than 10,000 unique, inactive genes waiting to be used, TIGM has the world's largest library of Black 6 genes, which are preserved at a chilling -346 degrees Fahrenheit in freezers containing liquid nitrogen.
Due in part to their unique genetic make-up, the mice within the facility's walls are not cheap — costing as much as $5,000 apiece. While college students may not have the budget for such a pet, scientists at Texas A&M and around the world use these genetically engineered mammals for their research.
"It may not sound flattering, but mice and humans are almost genetically similar," said Benjamin Morpurgo, TIGM's director of business and operations. "Ninety-eight percent of the genes found in mice are also found in humans."
This similarity has made mice a favorite testing model for predicting the potential effects that drugs and other medical treatments may have on humans. Moreover, Black 6 mice have been used in additional research such as understanding alcoholism and learning behavioral disabilities in humans.
Depending on the type of research, scientists may not require mice with any genetically similar significance. However, for scientists who need to understand how one particular gene reacts to certain drugs, these Black 6 mice are ideal candidates.
Binu Tharakan, assistant professor for the Department of Surgery in the A&M Health Science Center, uses knockout mice from TIGM to study the blood-brain barrier in mammals. Without these mice, Tharakan says he would not have a model for his study.
"The blood brain barrier protects the brain from various inflammatory molecules and certain bacterial infections," Tharakan said. "However, this barrier also prevents certain helpful drugs from reaching the brain. In order to understand and possibly treat conditions such as traumatic brain injury and stroke, we need to be able to pass drugs through the blood brain barrier. And these mice are allowing us to see exactly how the brain reacts to certain drugs."
One order, containing a single inactivated gene, includes four mice and costs $17,500 — before shipping costs that may range from $350 to $3,000 depending on the part of the globe to which the mice are destined.
"Our costs are mainly due to the labor and quality control that goes into producing these mice," Morpurgo said.
Simply put, these mice are far from simple to produce.
TIGM starts with frozen embryonic stem (ES) cells — cells taken from the early stage of a mouse embryo — containing the inactivated gene of interest. The ES cells then take six to eight weeks to thaw and expand. A highly-skilled microinjectionist then injects these cells into a protective cavity formed during embryogenesis, called a blastocyst, which is surgically placed in a recipient female mouse's uterus. Twenty-one days later, the mouse gives birth.
But this litter will not have the mice the scientists desire. The mice from this litter, known as chimeras, contain a mixture of DNA from the mother and the ES cells. These mice then mate with chimeras and this second generation has potential for a mouse that contains the gene of interest from the original ES cells.
Of the mice that are born from this second litter, a maximum of 33 percent may have the same gene as the ES cells, and these are the knockout mice. More often than not, the litter yields no knockout mice, which then requires further mating and more time.
"It's hard to guarantee success," Morpurgo said. "The fastest we have ever been able to produce a heterozygous mouse was in seven months. It really depends on the gene and some luck with the biology of the mice we choose to mate."
Since TIGM's move to College Station in August of last year, 15 unique knockout mice cycles have been completed. Two of these mice were made for professor of nutrition and food science, Robert Chapkin.