The transgenic Huntington's Disease mouse was developed by Gillian Bates, Ph.D., of Guy's Hospital in London, England, and her colleagues by introducing into the mouse's DNA the human Huntington's disease mutation, which was identified in a breakthrough discovery in 1993 after a decade-long research effort.
Called the R-6 strain, it is the first mouse model known to exhibit symptoms resembling chorea, the jerky, random muscular movements characteristic of Huntington's disease. The mice also experience epileptic seizures typical of juvenile onset of the disease, have decreased brain size, and suffer from a progressive loss in weight and muscle bulk. The mouse syndrome clearly results from introduction of the human mutation, although how closely the syndrome corresponds to human Huntington's disease is not yet established,
"This mouse represents the beginning of a revolution in the study of
Huntington's disease," said Nancy Wexler, Ph.D., President of the Hereditary
Disease Foundation (http://www.
The strain has been received into The Jackson Laboratory's Genetic Resources facility, the national center for mice that serve as models for human disease. Since 1993, at the request of the international research community, the facility has accepted more than 300 medically important new mouse models.
To insure their health and genetic integrity before widespread release for biomedical research, the mice are bred in a strictly controlled, disease-free environment at The Jackson Laboratory. Distribution begins when breeding colonies are sufficient in size.
"This very important model is just one example of the power of mouse genetics to provide new ways to approach treatment and ultimately to prevent human disease," said Kenneth Paigen, Ph.D., Director of The Jackson Laboratory. Among the hundreds of strains distributed by the Genetic Resources facility -- many of them developed through the Laboratory's own research -- are models for studying Down Syndrome, diabetes, obesity, leukemia, cystic fibrosis, hypertension, epilepsy, and glaucoma.
Huntington's disease is named for Dr. George Huntington, a physician who described "hereditary chorea" in 1872. Formerly known as Huntington's Chorea, the disease typically begins in mid-life, between the ages of 30 and 45, although onset may occur at any age. Males and females are affected equally, and it crosses all racial and ethnic boundaries.
In addition to the estimated 30,000 Americans with the disease, another 150,000 are "at risk," with a 50-50 chance they inherited Huntington's from an affected parent. Upon isolation of the gene in 1993, a predictive test was developed by which many people at risk can learn with a high degree of certainty whether they will develop the disease. Those who do not inherit Huntington's disease cannot pass it on to their children, and the chain of inheritance is broken.
The genetic cause of Huntington's disease has been found to be an abnormal expansion of a CAG (cytosine, adenine, guanine) nucleotide sequence in the coding region for the "huntingtin" gene on chromosome 4. This excess of trinucleotide repeats is characteristic of a number of other diseases, including Fragile X (the most common form of mental retardation), myotonic dystrophy, Haw River Syndrome, three types of hereditary ataxia, Machado Joseph disease, and Kennedy's disease (spinobulbar muscular dystrophy).
The Huntington's model was reported in Cell, Vol. 87, November 1, 1996. Co-authors with Dr. Bates were Laura Mangiarini, Kirupa Sathasivam, Mary Seller, and Martin Lawton, all of Guy's Hospital; Barbara Cozens and Stephen Davies of University College; Alex Harper, The Rayne Institute; Colin Hetherington, John Radcliffe Hospital; Yvon Trottier, Institut de Genetique et Biologie Moleculaire et Cellulaire; and Hans Lehrach, Max Planck Institut fur Molekulare Genetik.
Dr. Bates is Senior Lecturer in the Division of Medical and Molecular Genetics, United Medical and Dental Schools, Guy's Hospital. She has twice received the Lieberman Award of the Hereditary Disease Foundation in recognition of her research into Huntington's disease. The Hereditary Disease Foundation, located in Santa Monica, Calif., is a non-profit organization dedicated to the cure of genetic disease, with a focus on Huntington's disease.