<i>Tgr5</i><sup>-/-</sup> mice exhibited an attenuated ability to concentrate urine in response to dehydration, which was associated with decreased AQP2 expression in the kidney inner medulla.
Absence of functional cystic fibrosis transmembrane conductance regulator (CFTR) alters anion transport across CF airway epithelial cells and ultimately results in dehydration of the airway surface liquid.
For this reason we used two different approaches: i) a morphometric study, which consists in measuring the effect of dehydration on body and kidneys weights as well as the report kidney weight/body weight, ii) By immunohistochemistry, we proceed to study the effect of dehydration on the immunoreactivity of central vasopressin (AVP) and the kidney aquaporin-2 (AQP-2) which is a channel protein that allows water to permeate across cell membranes.
In CF airways, the lack of CFTR and increased ENaC activity lead to ASL/mucus dehydration that causes mucus obstruction, neutrophilic infiltration, and chronic bacterial infection.
Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration.
In CF, the loss of chloride transport caused by the mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel gene results in dehydration, mucus plugging, and reduction of the airway surface liquid layer (ASL) height which favour chronic lung infection and neutrophil based inflammation leading to progressive lung destruction and early death of people with CF.
However, when the body is dehydrated and needs to retain water, AQP2 relocates to the apical membrane, allowing water reabsorption from the urinary tubule into the cell.
Cystic fibrosis (CF) is caused by the loss of the cystic fibrosis transmembrane conductance regulator (CFTR) function and results in a respiratory phenotype that is characterized by dehydrated mucus and bacterial infections that affect CF patients throughout their lives.
Congenital nephrogenic diabetes insipidus (NDI) is a disorder associated with mutations in either the AVPR2 or AQP2 gene, causing the inability of patients to concentrate their pro-urine, which leads to a high risk of dehydration.
In vivo and in vitro studies demonstrated that CS rapidly decreased CFTR activity, leading to airway surface liquid (ASL) volume depletion (i.e., dehydration).
Underlying mutations in the CFTR (CF transmembrane conductance regulator) gene cause deregulation of ion transport and subsequent dehydration of the airway surface liquid, producing a viscous mucus layer on the airway surface of CF patients.
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.
Furthermore, the mutant AQP2 formed a heterooligomer with wild-type AQP2 and showed a dominant-negative effect on the normal apical sorting of wild-type AQP2 even under dehydration.
Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value because early diagnosis and treatment can avert the physical and mental retardation associated with repeated episodes of dehydration.
It is usually stated that in cystic fibrosis (CF), CF transmembrane conductance regulator protein abnormality results in imbalanced ion composition and dehydration of ASL, leading to abnormal rheologic and transport properties.