Disease relevance of TESC

• These results suggest that Gitelman syndrome requires 2 compound heterozygotic mutations and the coexistence of the large deletion in the C-terminal domain with Met672Ile substitution of the TSC could impair the transporter activity underling the hypokalemia and hypomagnesemia in this patient [1].
• Gitelman's syndrome (GS), an autosomal recessive disorder caused by a defect of the thiazide-sensitive Na-Cl cotransporter (TSC) at the distal tubule, is characterized by hyperreninemic hyperaldosteronism with normal or low blood pressure, hypokalemia, metabolic alkalosis, hypomagnesemia and hypocalciuria [2].

High impact information on TESC

• Over 88% of SNPs in the public (TSC and BAC overlap) and Celera databases were confirmed in independent resequencing [3].
• Mutation of the target sequence did not affect the ability of the cytoplasmic domain to bind carbonic anhydrase II or tescalcin but did affect calmodulin binding [4].
• Equilibrium dialysis with (45)Ca(2+) revealed that recombinant tescalcin binds approximately one Ca(2+) ion at physiological concentrations (pCa 4.5) [5].
• The tescalcin gene is preferentially expressed during mouse testis differentiation [5].
• Tescalcin also binds Mg(2+) (K(d) 73 microM), resulting in a much smaller fluorescence decrease [5].

Biological context of TESC

• One of them was a novel gene termed tescalcin that encoded a putative EF-hand Ca(2+)-binding protein [6].
• Based upon the localization of a 2.6 cDNA encoding the human TSC to chromosome 16q13, polymorphic markers spanning the region from 16p12 to 16q21 were tested for linkage to the Gitelman syndrome locus in three Dutch families with autosomal recessive inheritance of this disorder [7].
• PURPOSE: To evaluate the effect of a single treatment of contact diode laser transscleral cyclophotocoagulation (TSCP) on intraocular pressure (IOP) in patients with refractory glaucoma and perform a historical meta-analysis of the relationship between successful IOP control and various laser parameters [8].
• Mutant alleles result in loss of normal TSC function and the phenotype is identical to patients with chronic use of thiazide diuretics [9].

Anatomical context of TESC

• A novel regulatory protein, tescalcin (TSC), recently isolated from mouse embryonic testes, has been implicated in gonadal differentiation [10].
• Immunofluorescence studies indicated that TSC is prominent in cellular lamellipodia where it colocalizes with NHE1 [10].
• We also show that tescalcin is most abundant in adult mouse heart, brain, and stomach, as well as in HeLa and HL-60 cells [5].
• Tescalcin is expressed in the testis of Kit(W/W-v) mice, indicating that it is not dependent on the presence of germ cells [6].
• Functional studies point to a defect in the distal renal tubule in the thiazide-sensitive, electroneutral sodium-chloride co-transporter (TSC) [7].

Associations of TESC with chemical compounds

• Co-precipitation experiments demonstrated the interaction of human TSC with NHE1 in vitro and in vivo, and 45Ca(2+) overlay assay revealed that TSC binds Ca(2+) [10].
• The intrinsic tryptophan fluorescence of tescalcin was significantly reduced by Ca(2+), indicative of a conformational change [5].
• Cetirizine consistently reduced TSC and MSC scores after the first dose versus placebo (P < or = 0.001) and at most time points versus loratadine (P < or = 0.05) [11].
• We examined the thiazide-sensitive Na-Cl cotransporter (TSC) gene for the mutations that can be responsible for Gitelman's syndrome, and confirmed the diagnosis [12].

Analytical, diagnostic and therapeutic context of TESC

• These data suggest that epilepsy surgery may be beneficial in selected patients with TSC despite multifocal EEG and neuroimaging abnormalities [13].
• In summary, the membrane filtration technique with fluorogenic TSC agar showed the best performance characteristics of all the media tested as judged by their recovery efficiency and specificity in these water samples [14].

References