Aldose Reductase-Deficient Mice Develop Nephrogenic Diabetes Insipidus
| Title: | Aldose Reductase-Deficient Mice Develop Nephrogenic Diabetes Insipidus |
|---|---|
| Authors: | Ho, Horace T.B.; Chung, Sookja K.; Law, Janice W.S.; Ko, Ben C.B.; Tam, Sidney C.F.; Brooks, Heddwen L.; Knepper, Mark; Chung, Stephen S.M. |
| Publisher: | Molecular and Cellular Biology |
| Date Published: | August 01, 2000 |
| Reference Number: | 495 |
Aldose reductase (ALR2) is thought to be involved in the pathogenesis of various diseases associated with diabetes mellitus, such as cataract, retinopathy, neuropathy, and nephropathy. However, its physiological functions are not well understood. We developed mice deficient in this enzyme and found that they had no apparent developmental or reproductive abnormality except that they drank and urinated significantly more than their wild-type littermates. These ALR2-deficient mice exhibited a partially defective urine-concentrating ability, having a phenotype resembling that of nephrogenic diabetes insipidus.
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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)
To study ALR2's physiological functions, Ho, et. al., developed two lines of mice that were deficient in ALR2, and studied them. The mice showed no growth or reproductive abnormalities. In fact, these mice were no different in their appearance, weight, blood glucose levels and litter sizes than normal mice. However, the researchers noted that the mice deficient in ALR2 (called ALR2 knockout mice) could not concentrate their urine, and hence, they drank and voided excessive amounts of water. In short, ALR2 knockout mice develop nephrogenic diabetes insipidus (NDI).
The authors are not yet clear as to why an ALR2 deficiency leads to NDI. To date, the major known cause of NDI is either a lack of arginine vasopressin (AVP), an inability to respond to AVP, or a lack of aquaporin 2 (AQP2). The ALR2 knockout mice can synthesize and secrete AVP. They have normal levels of AVP receptors and AQP2. Still, the kidneys of these mice appear to have an impaired response to AVP. The authors speculate that further study of the ALR2 knockout mice may provide further understanding of the kidney's urine concentrating mechanism.