{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:38:25Z","timestamp":1790811505577,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,1,15]],"date-time":"2009-01-15T00:00:00Z","timestamp":1231977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:p>In humans, Dent's disease, an X\u2010linked renal tubular disorder, is characterized by low molecular weight proteinuria, aminoaciduria, glycosuria, hyperphosphaturia, hypercalciuria, nephrolithiasis, progressive renal failure and sometimes rickets or osteomalacia. The aetiology of X\u2010linked Dent's disease is established to be caused by mutations of the <jats:italic>CLCN5<\/jats:italic> gene. The protein product of this gene is the voltage\u2010gated chloride\u2013proton exchanger CLC\u20105. Previous studies by the Johns Hopkins group (Guggino) and the Hamburg group (Jentsch) have established that the <jats:italic>Clcn5<\/jats:italic> knockout mouse recapitulates the renal attributes of Dent's disease. In order to understand the changes in kidney function that accompany the knockout of the <jats:italic>Clcn5<\/jats:italic> gene, we examined gene expression profiles from dissected proximal segment 1 (S1) and segment 2 (S2) tubules of mouse kidneys. Overall, 725 genes are expressed differentially in the proximal tubules of the Dent <jats:italic>Clcn5<\/jats:italic> knockout mouse model compared with those of control wild\u2010type mice. A major finding is the change in the cholesterol synthesis pathway. Some interesting changes also occur in genes encoding transport proteins. One of these transport proteins, the sodium bile cotransporter gene, <jats:italic>Slc10a2<\/jats:italic>, has transcripts increased by 17\u2010fold in the <jats:italic>Clcn5<\/jats:italic> knockout mouse. The Clc\u20103 protein encoded by <jats:italic>Clcn3<\/jats:italic>, a chloride\u2013proton exchanger related to Clc\u20105, has a 1.9\u2010fold increase in transcripts. The Npt2c protein, a proximal tubule sodium phosphate cotransporter encoded by <jats:italic>Slc34a3<\/jats:italic>, has a 0.6\u2010fold decrease in the number of transcripts. The sodium\u2013proton exchanger\u2010like protein, Nhe10\/sperm, encoded by <jats:italic>Slc9a10<\/jats:italic>, has a 0.5\u2010fold decrease in transcript number. These genes are discussed with regard to the possible physiological outcomes of their transcript or protein changes.<\/jats:p>","DOI":"10.1113\/expphysiol.2008.044586","type":"journal-article","created":{"date-parts":[[2008,10,18]],"date-time":"2008-10-18T00:49:27Z","timestamp":1224290967000},"page":"191-196","source":"Crossref","is-referenced-by-count":11,"title":["Can we generate new hypotheses about Dent's disease from gene analysis of a mouse model?"],"prefix":"10.1113","volume":"94","author":[{"given":"Sandra 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