Researchers at Johns Hopkins Medicine and Tottori University in Japan have genetically altered and characterized what they believe to be the first rat model of Down syndrome.
The American Journal of Human Genetics published a report of their findings on January 24.
Scientists have long sought ways to improve medical care for people with Down syndrome, particularly those who suffer from the physical and mental difficulties that shape the condition. These include a higher risk of heart defects, gastrointestinal difficulties, and difficulties with learning and memory.
According to Roger H. Reeves, a doctor in physiology at the Johns Hopkins University School of Medicine, developing an animal model that integrates these features with human Down Syndrome will enable us to run more efficiently.
Down syndrome is the result of a so-called chromosomal trisomy, or tripling. A typical human cell has 23 pairs of chromosomes, which explain its internal processes and how it interacts with the rest of the body. It occurs when a person is born with an extra partial or whole copy of the 21st chromosome, a condition called trisomy 21. It''s effects vary among individuals.
Rats do not exist as humans randomly produce offspring with additional 21st chromosomes, so the researchers decided to undertake a complicated task of genetic engineering to produce rats with an additional 21st chromosome.
The 21st chromosome was transferred from human white blood cells to mouse cells, then to chicken cells, then hamster cells, and, finally, into a rat embryo.
The researchers made many changes at each transfer, including the addition of a green glowing protein, which under ultraviolet light identified rats with additional 21st chromosomes.
Reeves and his team then examined the genetically engineered rats'' cognition and physical characteristics for traits associated with an additional 21st chromosome.
For example, researchers conducted standardized maze tests with the genetically engineered rats to test rats learning and memory.
Rats with an extra 21st chromosome took longer to solve the maze than genetically typical rats. They also had difficulties remembering the mazes solution when they were challenged to solve the same puzzle for four days.
Other cognitive tests imply that the rats with an extra 21st chromosome were more anxious and hyperactive than rats without the extra chromosome. These results are consistent with studies in people with Down syndrome, who indicate higher levels of anxiety, attention disorders, and learning and memory impairments.
In anatomical studies, researchers found that a brain structure called the cerebellum was significantly smaller in rats with an additional 21st chromosome. The cerebellum is essential to the body''s core functions, including message processing across the brain, and is significantly smaller in people with Down syndrome.
According to Reeves, there have already been advances in the development of drugs that help the cerebellum grow in mice. If we eventually transform it into medicines for humans, we may be able to assist people with Down syndrome in improving their ability to learn and become cognizant.
Some people with Down syndrome were unable to see a rat and determine whether its face was different from a typical rodent, but a computer program may discern these differences. The skulls were scanned in a CT machine, and the data was added to a computer simulation program, which showed that the rats had reduced their facial appearances. The distinct facial differences in the rats were also observed in humans.
Finally, 17 percent of rats with an additional 21st chromosome had an abnormality of heart ventricles that is similar to one diagnosed in up to 21% of children with Down syndrome.
The model will be distributed to scientists through the National Rat Resource and Research Center at the University of Missouri and the National BioResource Project for the Rat in Japan.