As Time Goes by, Mutant Mice Face Problems

By Travis, J. | Science News, March 13, 1999 | Go to article overview

As Time Goes by, Mutant Mice Face Problems


Travis, J., Science News


Mice lacking an important enzyme go gray and lose their hair earlier than normal, frequently develop sores as they age, and have unusually short life spans. They also suffer more tumors than normal mice do, raising questions about a much-hyped idea for treating cancer.

These age-related conditions showed up in a new long-term study of mice that have a mutation in a gene for telomerase, an enzyme that affixes protective DNA segments to ends of chromosomes. Scientists know that if this enzyme doesn't work, the chromosomal tips, called telomeres, usually shorten whenever a cell divides, ultimately disappearing.

In 1997, Ronald A. DePinho of the Dana-Farber Cancer Institute in Boston, Carol Greider of Johns Hopkins Medical Institutions in Baltimore, and their colleagues described the development and surprisingly healthy early life of six successive generations of mice that lacked telomerase. Each generation had shorter telomeres than the previous one, and the sixth turned out infertile (SN: 10/11/97, p. 228).

Now, in the March 5 CELL, the scientists describe what happens as these mutant mice age and their telomeres shrink further in many cells. "Over the course of their 2-year lives, [the mice] walk this telomere plank into genetic instability, loss of cell viability, and so on," says DePinho.

A few scientists have speculated that many ravages of aging result because telomeres shrink over time in mammalian cells. Yet as the telomerase-lacking mice grew older, they didn't experience a greater-than-normal incidence of some age-related conditions, such as osteoporosis, cataracts, and atherosclerosis.

Nonetheless, telomere shortening may play a role in certain aspects of aging. In addition to premature graying and hair loss, the aging mutant mice have an increased rate of skin ulcers and are slower than normal to heal wounds--traits also common in elderly people. …

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