The means of coping with environmental adversities are often compromised in aged mammals. Responses of older people to inflammation, to toxicity of metals, and to hormonal alterations frequently differ from those of the younger population. The genes encoding human transferrin and haptoglobin respond to these three environmental directives, and thus will be ideal to study in an aging background. The transgenic mouse model provides the biological background to analyze the expression of chimeric human genes during aging. The mouse is well into the aging process within 24 to 28 months after birth. By modulating human transferrin and haptoglobin chimeric genes with hormones, inflammatory signals or heavy metals, responding factors and the DNA or RNA sequences they interact with can be identified. Thus, the transgenic mouse model can provide, in a relatively brief period, information about the molecular basis of gene response to environmental adversities during aging. Transferrin circulates throughout the body contributing to homeostasis by its capacity to transport and donate iron to appropriate tissues. It is important in the brain where it protects tissues from heavy metal toxicity, especially in aging when increased levels of heavy metals accumulate there. Haptoglobin is synthesized by the liver and binds free hemoglobin released by aged or injured red blood cells. It protects the kidney from damage following hemolysis, a condition often related to hemolytic anemia in older people. In inflammation, haptoglobin, a positive acute phase reactant, increases in plasma concentration. In health elderly people haptoglobin is also reported to increase. Haptoglobin will serve, therefore, as a model for the expression of positive acute phase reactants which are reported to increase slightly but significantly in healthy older people. It will be of interest to determine whether the same, or different, DNA sequences in the human haptoglobin gene respond to inflammation and aging. The transgenic mouse presents a useful experimental model to analyze in vivo the expression of a human chimeric gene within an aging mammalian system.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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University of Texas Health Science Center San Antonio
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