Generation and phenotypic analysis of mice lacking all urea transporters

摘要: Urea transporters (UT) are a family of transmembrane urea-selective channel proteins expressed in multiple tissues and play an important role the urine concentrating mechanism mammalian kidney. UT inhibitors have diuretic activity could be developed as novel diuretics. To determine if functional deficiency all UTs causes physiological abnormality, we established mouse model which were knocked out by deleting 87 kb DNA fragment containing most parts Slc14a1 Slc14a2 genes. Western blot analysis immunofluorescence confirmed that there is no expression urea transporter these all-UT-knockout mice. Daily output was nearly 3.5-fold higher, with significantly lower osmolality mice than wild-type All-UT-knockout not able to increase urinary concentration after water deprivation, acute loading, or high protein intake. A computational simulated UT-knockout models identified individual contribution each mechanism. Knocking also decreased blood pressure promoted maturation male reproductive system. Thus, caused urine-concentrating defect little abnormality extrarenal organs.