Lessons from Transgenic Mouse Lines Expressing Sickle Hemoglobin

Abstract

Conclusions and Future Work

The transgenic mice lines already developed have a significant potential to increase our understanding of the pathogenesis of kidney, lung, and retina damage in sickle-cell anemia. Second generation transgenic mice, interbreeding of existing lines, promise to improve this score even more. The capacity of eliciting sickle complications by hypoxic treatment renders these animals particularly useful in the study of the renal concentration defect and priapism.

While the shortcomings of the transgenic models (i.e., when mice do not behave as humans) have discouraged those who naïvely expected a “perfect” model, they also have the potential of furthering our comprehension of the disease, by allowing replacement experiments and by exposing the relative importance of pathogenic determinants.

Even the less severe phenotypes among the transgenic mouse model will demonstrate their usefulness. A panoply of different levels of severity will assist in the study of specific pathogenic mechanisms, since solid predictions can be in a graded field of subjects.

Finally, the transgenic models are in the early stage of their use as test sites for pharmacological intervention (52), and this is an area likely to expand rapidly and be fruitful.

The work on transgenic mice at Einstein has been funded by grants by the NIH (HL38655) and the American Heart Association, NYC affiliate. I am greatly indebted to my collaborators in this endeavor, Mary E. Fabry, Frank Costantini, Dhananjaya K. Kaul, Gerard Lutty, Mitzy Canessa, Sandra Suzuka, Norman Bank, Haig Aynedjian, Stephan Factor, Jose Romero, Han-Mou Tsai, Edward M. Rubin, James Hofrichter, D. S. McLeod, A. Seetharama Acharya, Rajendra P. Roy, and G. W. Christoph.