PMC:1189073 / 9662-11442 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1189073","sourcedb":"PMC","sourceid":"1189073","source_url":"http://www.ncbi.nlm.nih.gov/pmc/1189073","text":"mice produce very dilute urine (Figure 1D). Basal urine concentration in mutant mice is about 161 mOsm, compared to about 1,293 mOsm in wild-type mice (p \u003c 0.001). Normally, urine concentration is under the control of the hypothalamus, which, in response to hypovolemia or hypernatremia [21], secretes AVP. The synthetic AVP analog, 1-deamino-8-D-arginine vasopressin (dDAVP; also called desmopressin), is a potent agonist of AVPR2. When administered to wild-type mice, dDAVP leads to a dramatic increase in urine concentration, from 1,293 to 5,885 mOsm (4.6-fold; Figure 1D). With similar treatment, mutant mice concentrate their urine to a lesser but still significant extent, from 161 to 470 mOsm (2.9-fold), indicating that these animals are not only unable to concentrate their urine properly but are also defective in their response to dDAVP. The smaller response to dDAVP indicates some residual activity of the mutant AQP2 channel, which must be sufficient to allow survival of the individual, in contrast to the T126M knock-in mouse [18].\nMultiple heterozygous matings yielded 101 animals, which appeared at a ratio of 26:49:26, near the expected Mendelian wild type, heterozygote, and mutant frequencies, respectively, indicating that there is no reduced viability associated with this mutation. Other than the increased urine production and water intake, there was no overt phenotype in mutant mice, save distended kidneys, which appeared variably in adult animals (Figure 2A). Although not specifically measured, mutant mice seem to have a normal lifespan. The one animal that was followed lived to 18 mo, typical for animals in our colony.\nFigure 2 Anatomy and Histology of Mouse Kidneys\n(A) Gross anatomy of an affected mouse (8-mo-old male). This shows the 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