At first, the team though that a mistake had been made--that the gene had simply not been deleted in this mouse. But when they looked at the thymus in these mice, they found, to their surprise, that it was abnormal but still made some T-cells.
Manley instantly knew that the lab mistake was a golden opportunity. It showed for the first time that the role of the nude gene in T-cell production is far more complicated than previously thought.
The specific cells in the thymus required for T-cell maturation are thymic epithelial cells (TECs). In the mutant nude mouse, these TECs fail to grow and mature, so no T-cells are made. But in the mutant made in Manley's lab, the thymus did produce T-cells, although in greatly reduced numbers.
It turned out that the initiation and progression of TEC growth are genetically separable functions in the new mutant mouse. In addition, the team provided the first genetic evidence that an already-known process called "crosstalk" is needed for the growth of the thymic epithelial cells.
"Normal nude mice never even start to develop T-cells, because the TE cells remain immature," said Manley. "These mutants are now telling us how TE cell differentiation occurs. This is the first nude mutant that can produce partially functional TE cells and as a result can also make some T-cells. Now we have to figure out how it happens."
The practical applications of the research are considerable. The action of the thymus in producing mature disease-fighting T-cells peaks in a person's mid-teens and then slowly erodes. This is one reason why older people and babies are frequently sickened by or die from diseases that cause little harm to those from their teenage years to midlife.
Likewise, certain diseases can kill off T-cells, making the bod
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Contact: Kim Carlyle
kcarlyle@uga.edu
706-583-0913
University of Georgia
5-Oct-2003