| Urea transporter(UT) proteins are central to modulating urea movement across biological membrane and their major physiologic role are in the urinary concentrating mechanism. To date, all of the known facilitative UT proteins are the product of two genes, UT-A(Solute Carrier Family 14α2, slc14α2) and UT-B(slc14α1). The two UT genes occur in tandem on chromosome 18q12-21. UT-B is strongly expressed in red blood cells and kidney ,also many non-renal tissues, such as heart, brain. The clinically important Kidd(JK) blood group antigens are carried by the UT-B in red cells, and Human Lacking of JK antigen are also called Jknull . Some Jknull phenotype individuals of Asian, Australian, French, Finland and Polynesian have been identified but it has a very low frequency in other populations. And to date, there is not any report about the happeness of Jknull in chinese population. Jknull RBCs are easily screened out by increased resistance to lysis in 2 M urea solution. Although major steps have been made in defining the molecular identity and basic functional characteristics of UT-B, but little information was known about their physiological function. The research based on Jknull phenotype or UT-B gene knock-out animal model was the most important tool for the study of UT-B function. In UT-B knockout mice, the urine concentrating ability was reduced , due to the block of urea counter-current exchange. The reported Jknull phenotype is not associated with any obvious clinical syndrome, except for a urine-concentrating defect. There is no report about The effect of UT-B absence on the other organ's function Objective : In this study, we using 2M urea solution hemolysis test screen out a UT-B absent individual with Progressive Familial Heart Block (PFHB I). study on the genotype and phenotype of Propositus his erythrocyte membrane lack the permeability, in order to find out the relation between UT-B absence and disease. Methods: (1) The individual involved in this study was Jk(a-b-) individual who was screened out from in-patients using 2 M Urea hemolysis test, and his family were also suffered from Progressive Familial Heart Block. Contrast group were health people. (2) Phenotype of this family were identified by examining blood samples using Indirect Antiglobiulin Test. (3) Urea and Water permeability in erythrocytes was measured by stopped-flow light scattering. The difference of Urea and Water permeability in human and mice was compared. (4) Molecular genetics analysis of the genome DNA of this kindred was done by PCR and DNA sequencing. (5) Some testes including routine test of blood and urine sample, ionic test, biochemical test, liver functional test, renal functional test of this kindred were done. (6) The clinical history was investigated in order to analyse clinical phenotype of this kindred.(7)The effective of UT-B specific inhibitor Ploretin on the extent and rate of cultured rat ventriculo-myocardium was observed.(8)The effective of Ploretin on AP parameters (APA, RMP), L-type Ca2+ channel and inward rectification K current (IK1) of ventricular myocytes were studied using whole-cell patch-clamp method.Results:(1)Only one JK(a-b-)phenotype individual was screened from 20000 patients. The normal red blood cell swelled and lysed quickly in 2 M urea solution. But the red blood cell of Propositus shrunk first in same solution and then swelled slowly, appearing an character of increased resistance to lysis in 2 M urea solution.(2)Urea permeability was reduced 120 fold in Propositus's erythrocytes.(3)DNA sequencing showed that two different mutations on the codon between intron 5 and exon 6 of the two allele of UT-B were found in this patient (AGG→ACC；AGG→AAG), which leading to the deletion of exon 6 after transcription. He was heterozygote with two mutation. (4) His sister and children was heterozygote (AGG→ACC；AGG), had a same mutation (AGG→ACC) in one allele. Their phenotype of erythrocyte was JK(a+b+)and JK(a-b+) respectively. The urea permeabili...
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