The monkey model of Huntington's Chorea
Choreal rhesusAlexey Levin, Voice of America
This disease (in the Russian-language literature it is more often called in the old way, Huntington's chorea – VM) has been known for more than 130 years, but scientists came closer to understanding its nature only after the advent of modern genetics and molecular biology.
On February 15, 1872, a young American therapist George Huntington, who practiced in the outback of Ohio, made a report at a meeting of the local medical society, which was destined to go down in the history of medicine. In this short message, the symptoms of a strange disease, which Huntington called hereditary chorea, were very accurately described.
At that time, chorea was called a variety of pathologies, united by a single sign. Their victims, in addition to their desire, made shaking movements of the head, face or limbs. Hence the name: the Greek word "chorea" means "dance". Huntington came to the conclusion that the form of chorea he noticed was fraught with degenerative changes in the psyche and, moreover, was highly likely to be transmitted from parents to children. Two months later, his work was published in the Philadelphia journal Medical and Surgical Reporter. After that, the medical community became interested in the new disease, which gave it the name of the discoverer.
Modern medical reference books say that Huntington's disease is a hereditary disease that leads to impaired coordination of movements, memory loss, mental degradation and premature death. The disease affects about one out of every 10 thousand people, and its symptoms mainly manifest themselves in middle age. If one of the parents suffers from Huntington's disease, then the chances of a newborn child being a victim of it are 50%.
This pattern was established a long time ago. With the formation of medical genetics, its meaning also became clear – the dominant gene mutation is at the heart of the disease. In 1993, it was proved that it is localized within a single gene located on the fourth chromosome. This gene is responsible for the synthesis of a protein called huntingtin.
Its molecule includes a fragment containing a chain formed from repeating molecules of the amino acid glutamine. In healthy people, the number of such repeats ranges from 8 to 35, and carriers of the mutant gene have 36 or more. This excess of glutamine turns harmless huntingtin into a powerful weapon that destroys nerve tissue.
Scientists do not yet know what the role of the normal form of huntingtin is, but its absence is incompatible with life. Mice with the huntingtin gene disabled die in the womb. Modern medicine makes it easy to detect the presence of a mutant huntingtin gene in a human embryo, but its possibilities end there. Victims of this disease, as a rule, die no later than 15-20 years after the manifestation of its first symptoms.
Neuroscientists have long been trying to find opportunities to study the development of Huntington's disease in animals. Some of its features can be reproduced in transgenic mice, which are endowed with a defective version of the human huntingtin gene. However, these results are of limited value, since rodents differ greatly from humans in both genetics and physiology. It would be much more useful to study this disease on the closest relatives of humans, primates. However, no one has succeeded so far.
Now this milestone has been crossed. The staff of the Yerkes National Center for Primatological Research, together with colleagues, have fully constructed rhesus monkeys with the human huntingtin gene in its mutant form. To do this, they first embedded this gene into the unfertilized eggs of monkeys using a viral carrier. The eggs were then artificially inseminated and implanted into the wombs of eight females of this species.
Three of them gave birth to five cubs carrying an abnormal version of the huntingtin gene. Of these five, two survived, now they are already 10 months old. One of the monkeys has already noticed involuntary limb movements and muscle spasms, typical symptoms of the early stage of Huntington's disease. The second macaque still looks healthy.
The significance of this work goes far beyond modeling Huntington's disease. This is generally the first example in the history of science of the creation of transgenic primates carrying a pathological version of the human gene. So the achievement of Anthony Chan and his colleagues opens the way to the construction of monkeys with altered heredity, on which it will be possible to study other human diseases caused by genetic abnormalities.
Portal "Eternal youth" www.vechnayamolodost.ru27.05.2008