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A little telomerase isn't enough

With seed money from Johns Hopkins Institute of Cell Engineering, a Johns Hopkins geneticist and her team have discovered a critical link between the health of stem cells and the length of the chromosome ends within them.

Chromosome ends, or telomeres, are repetitive stretches of DNA that protect chromosomes in much the same way as plastic tips on shoelaces prevent the fabric from fraying. Each time a cell divides, its chromosome ends get a little shorter, and eventually the cell can no longer divide because its critical genetic information is exposed. In stem cells, however, a protein called telomerase normally maintains the telomeres' length, allowing the cells to divide indefinitely.

Now, the Hopkins researchers report that mice engineered to have just half the normal amount of telomerase can't maintain their stem cells' chromosome ends, showing that a little telomerase isn't enough. In these "half-telomerase" mice, their telomeres shortened over time, bringing an early demise to stem cells that replenish the blood supply, immune system and intestine, the researchers report. Moreover, offspring of these mice bred to have normal levels of telomerase still exhibited early loss of stem cells, the researchers report in the Dec. 16 issue of Cell.

"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, Ph.D., director and professor of molecular biology and genetics in the Johns Hopkins Institute of Basic Biomedical Sciences. "This phenomenon could complicate the hunt for disease genes."

Scientists generally figure that inherited disease accompanies an inherited mutation in one or more genes. In the case of the genetically normal offspring of two half-telomerase parents, however, the disease is still present. The problem in these animals turns out to be the animal's inherited telomere length, not the s
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Source:Johns Hopkins Medical Institutions


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