Carol Greider, Ph.D., director and professor of molecular biology and genetics in the Johns Hopkins Institute of Basic Biomedical Sciences and colleagues have found that the length of telomeres is important in ensuring that stem cells are able to divide indefinitely.
Telomeres are the ends of the chromosomes that protect genetic information while the chromosome is undergoing division. These are basically "repetitive stretches of DNA" designed to protect chromosomes. Every time a cell undergoes division, the chromosome ends shorten ultimately exposing the genetic information in the stem cell and preventing further division. But a protein called telomerase prevents this from happening and thus cells can divide "n" number of times. In the current study, the Johns Hopkins researchers say that stem cells did not retain their chromosome ends in mice that were engineered to have just half the normal amount of telomerase. "These offspring have what we have called 'occult' genetic disease -- their genetic make-up is perfectly normal, but they still have the physical problems of their parents," says Carol Greider. "This phenomenon could complicate the hunt for disease genes." The problem is that offspring inherit diseases through mutations in genes, but even in half-telomerase mice the disease is still present although the genetic basis gets obscured due to the inherited telomere length and not the gene. "If you were to search for the genetic mutation behind this mouse's disease, you wouldn't find it -- there isn't one," says Greider. "These mice develop disease only because their telomeres are short, and having telomerase doesn't lengthen them right away." The condition in these altered mice bears a close resemblance to dyskeratosis congenita in humans where stem cells in the bone marrow as well as in the intestine are unable to multiply as required and consequently die early.
AdvertisementThe details of the study are published in the December 16 issue of the journal Cell.
The study was funded by the National Institutes of Health and the Johns Hopkins Institute for Cell Engineering. Authors on the paper are Hao, Armanios, Greider, Margaret Strong, Baktiar Karim, David Felser and David Huso, all of Johns Hopkins School of Medicine. Karim and Huso are with the Department of Comparative Medicine.
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