Mice born with extra copies of a human gene develop learning defects that may resemble those in Down syndrome. The finding, reported in this month's issue of Nature Genetics, could shed light on this condition, which strikes about one in 800 babies when they inherit an extra piece of chromosome 21--and extra copies of all the genes on that fragment.
These children are born with a bewildering variety of defects: from cosmetic blemishes such as cleft palate to severe impairments in learning ability, immune function, and heart development. Hoping to understand how the extra chunk of chromosome 21 can result in such physiological chaos, a team led by geneticist Edward Rubin of the Human Genome Center at Lawrence Berkeley National Laboratory in California created four lines of transgenic mice. Each was equipped with extra copies of a different subsection of the human chromosome 21 region that crops up in all Down syndrome cases.
Rubin's team tested for one defect, learning impairment, in the mice. The researchers put the mice through a standard test in which the animals are trained to find a platform in a swimming pool. The platform is then removed. The longer the mice look for the platform at its former site, the better they are thought to have memorized the location. Mice with one particular extra section of the human chromosome spent significantly less time hunting for the platform in its original location than did mice carrying other chromosome portions. In further experiments, the mice with this chromosome section also had a harder time memorizing a new platform location.
The less adept mice, Rubin's team found, carry extra copies of a previously known human gene called DYRK; a mutated version of an almost identical gene in fruit flies, called minibrain, causes neurological defects. DYRK, Rubin offers, "may be an important player in a limited number of players" in Down syndrome. Other experts agree. Says David Kurnit, a geneticist at the University of Michigan Medical Center in Ann Arbor, "I think it will turn out that [the gene] is very important in understanding Down syndrome."