Nephrogenic Diabetes Insipidus in Mice Lacking All Nitric Oxide Synthase Isoforms
|Title:||Nephrogenic Diabetes Insipidus in Mice Lacking All Nitric Oxide Synthase Isoforms|
|Authors:||Morishita, Tsuyoshi; Tsutsui, MD, PhD, Masato; Shimokawa, Hiroaki; Sabanai, Ken; Tasaki, Hiromi; Suda, Osamu; Nakata, Sei; Tanimoto, Akihide; Wang, Ke-Yong; Ueta, Yoichi; Sasaguri, Yasuyuki; Nakashima, Yasuhide; Yanagihara, Nobuyuki|
|Publisher:||Proceedings of the National Academy of Sciences of the United States of America|
|Date Published:||July 26, 2005|
You may, however, read this article at the Proceedings of the National Academy of Sciences of the United States of America website.
To return to this page, use your "back" key.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
Because the NO synthase isoforms can compensate for each other should one be low in number, the ultimate role each plays in the human body is not clear. Morishita, et al., developed a line of mice that lack all three NO synthase genes, and therefore they have no NO in their bodies. Although these mice had a normal appearance, they had low survival and fertility rates. Further, these mice all developed NDI. When the researchers examined the kidneys of these mice, they found that the amount of cyclic adenosine monophosphate (cAMP) produced, in response to vasopressin stimulation, and the number of aquaporin-2 (AQP2) proteins were much lower than usual. In addition, lesions developed within the fine tubular structure of the kidneys.
Previous studies have indicated that NO both stimulates cAMP production and promotes AQP2 insertion into the membrane of collecting duct cells in the kidney. The work of Morishita, et al., confirmed the necessity of NO in these processes. In these mice, the functional abnormalities of NDI appeared before the occurrence of the structural abnormalities associated with NDI. Thus, the NDI in these mice appears more like inherited NDI than the acquired form of the disease.
The researchers conclude that NO plays a pivotal role in maintaining balance and stability in the body, especially in the kidneys.