#2640 SINGLE TUBULE RNASEQ FROM GITLEMAN SYNDROME MICE REVEALING MAGNESIUM HANDLING IN DISTAL RENAL TUBULES

Abstract Background and Aims Gitelman syndrome (GS) is characterized by salt-losing hypotension, hypokalemic metabolic alkalosis, hypomagnesemia, hypocalciuria caused a specific mutation in the thiazide-sensitive sodium chloride co-transporter (NCC) gene SLC12A3. However, magnesium (Mg2+) associated distal renal tubules remains unclear. Method We performed small samples RNA-seq from manual microdissection of convoluted (DCT1s) nonsense Ncc Ser707X (S707X) homozygous knockin mice (NccS707X/S707X mice) (n = 4) wild-type (WT, n 4). Cortical thick ascending limbs Henle (cTALs), connecting tubule (CNT), cortical collecting duct (CCD) were also microdissected. Results Among DCT makers, Slc12a3 Pvalb (Parabumin) significantly downregulated (Log2TPMS707X/WT: −4.45, P 0.0003; −6.888258295, 0.0003, respectively). Mg2+ transporters Trpm6 expression downregulated. In addition, Egf Cnnm2 have been reported to increase TRPM6 trafficking or activity, decreased segment. Rack1 was DCT1. Claudins including Cldn10, Cldn16, Cldn19, involving paracellularly reabsorption Ca2+and Mg2+, not changed cTALs. All findings indicate chronic hypokalemia may mediate DCT1 remodeling affect development. Conclusion Our RNA-Seq dissected highlight possible molecular pathway hypomagnesemia GS. Chronic inactivation Slc12A3 development causing loss transporters.