May 15, 2003 Researchers from the National Cancer Institute (NCI) have developed a mouse model of the premature aging syndrome known as Hutchinson-Gilford Progeria Syndrome (HGPS), according to a report appearing in the journal Nature. Researchers hope the mouse model will facilitate a better understanding of the fatal syndrome, as well as provide clues to the normal aging process.
Currently, there is no treatment for progeria, and children with the rare condition usually die of heart disease in their early teens. Although normal at birth, children with progeria begin to develop growth retardation, thinning skin, and fragile bones as young as 18 months.
"The similarities between mice with this particular mutation and patients with progeria are remarkable," said Colin Stewart, Ph.D., of NCI's Center for Cancer Research, the senior investigator on the study. "Now that we've identified the critical gene and have an animal model that mimics progeria, we have powerful tools for studying both the aging process and this devastating disease."
The results of the animal study come less than a month after the announcement that scientists have discovered the gene responsible for progeria in children. Studies published in March in the journals Science and Nature described a single inaccuracy in the Lamin A (Lmna) gene that appears to account for the syndrome. The gene produces structural proteins known as lamins, which are found in the cell nucleus. In the new study, NCI researchers report that mice with a specific mutation in the same gene have symptoms remarkably consistent with those of progeria patients.
Although indistinguishable from their littermates at birth, mice with the Lmna mutation develop severe growth retardation early in life and die within five weeks, whereas normal mice generally live up to two years. Like progeria patients, mice in the study showed signs of premature aging.
In the mice, accelerated aging was most apparent in the skin, which thinned dramatically and lost hair. Researchers also observed reduced growth or degeneration of the heart and skeletal muscles in mutant mice. Similarly, the mice had either incomplete development of the skeleton or a premature loss of bone mass, also characteristic of children with progeria. Mice with the Lmna mutation shared many other symptoms with progeria patients, including a slight waddling gait, abnormal teeth, and incomplete sexual maturation.
The Lmna gene codes for A- and C-type lamins, components of the fibrous network lining the inside of the cell nucleus called the nuclear lamina. The mutant form of the gene associated with progeria symptoms causes disruption in the structure of the cell nucleus. Studying the relationship between progeria symptoms and this abnormality could help researchers understand the cellular processes associated with aging.
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