Mouse model of type II Bartter's syndrome. I. Upregulation of thiazide-sensitive Na-Cl cotransport activity

摘要

Nevertheless, the high survival rate of our inbred Romk mice suggests that specific genes have been selected which could have mitigated fluid and electrolyte losses. Consequently, the selected adaptive changes in the Romk mouse could have altered the mouse phenotype compared with that observed in HPS. Diuretic pharmacotyping has been used to separate the various phenotypes of hypokalemic renal salt-wasting disorders (22) and can be used to compare responses in Romkr mice and type II HPS. The differential sensitivities to diuretics has established that the defect in HPS was localized to the TAL (25). Thus individuals with HPS exhibit impaired diuretic and natriuretic responses to furosemide, while the effect of this diuretic in Gitelman's disorder is normal (22). In contrast, individuals with Gitelman's disorder exhibit a markedly reduced response to thiazide diuretics that inhibit the thiazide-sensitive NaCl cotransporter localized in the distal convoluted-tubule (DCT), while the response to this diuretic is exaggerated in HPS.