Kotnik Primoz, Battelino Tadej, Debeljak Marusa, Podkrajsek Katarina Trebusak, Waldhauser Franz, Frøkiaer Jørgen, Nielsen Søren, Krzisnik Ciril
Department of Endocrinology, Diabetes and Metabolism, University Children's Hospital, Vrazov trg 1, SI-1000 Ljubljana, Slovenia.
J Pediatr Endocrinol Metab. 2007 Apr;20(4):483-9. doi: 10.1515/jpem.2007.20.4.483.
Activation of the V2 receptor by arginine vasopressin (AVP) results in trafficking of the water channel AQP2 to the luminal plasma membrane and a small amount into the urine. Mutations in the A VPR2 gene, encoding the AVP V2 receptor, result in congenital nephrogenic diabetes insipidus (CNDI). To determine a correlation between A VPR2 mutations and urinary AQP2 excretion, immunobloting was used to detect AQP2 in the urine of patients with CNDI before and after a dehydration test. The patients' genotype was determined using PCR amplification and direct sequencing of the complete A VPR2 gene. Urinary AQP2 excretion was absent in patients with severely debilitating mutations, a novel total deletion of the A VPR2 gene, and a novel nonsense mutation W296X. However, it was detected in siblings with a V88M missense mutation. Urinary AQP2 excretion correlated well with other tested phenotype markers. Urinary AQP2 excretion could be used to evaluate the remaining in vivo integrity of the AVP-V2 receptor-AQP2 cascade in patients with CNDI.
精氨酸加压素（AVP）激活V2受体可导致水通道蛋白2（AQP2）转运至管腔质膜，并少量进入尿液。编码AVP V2受体的AVPR2基因突变会导致先天性肾性尿崩症（CNDI）。为确定AVPR2突变与尿AQP2排泄之间的相关性，采用免疫印迹法检测CNDI患者脱水试验前后尿液中的AQP2。通过PCR扩增和对完整AVPR2基因进行直接测序来确定患者的基因型。严重致残性突变患者、AVPR2基因新的完全缺失患者以及新的无义突变W296X患者的尿AQP2排泄均缺失。然而，在具有V88M错义突变的同胞中检测到了尿AQP2排泄。尿AQP2排泄与其他检测的表型标志物相关性良好。尿AQP2排泄可用于评估CNDI患者体内AVP-V2受体-AQP2级联反应的剩余完整性。
