V2 vasopressin receptor deficiency causes changes in expression and function of renal and hypothalamic components involved in electrolyte and water homeostasis.
Polyuria, hypernatremia, and hypovolemia are the major clinical signs of inherited nephrogenic diabetes insipidus (NDI). Hypernatremia is commonly considered a secondary sign caused by the net loss of water due to insufficient insertion of aquaporin-2 water channels into the apical membrane of the collecting duct cells. In the present study, we employed transcriptome-wide expression analysis to study gene expression in V2 vasopressin receptor (Avpr2)-deficient mice, an animal model for X-linked NDI. Gene expression changes in NDI mice indicate increased proximal tubular sodium reabsorption. Expression of several key genes including Na+-K+-ATPase and carbonic anhydrases was increased at the mRNA levels and accompanied by enhanced enzyme activities. In addition, altered expression was also observed for components of the eicosanoid and thyroid hormone pathways, including cyclooxygenases and deiodinases, in both kidney and hypothalamus. These effects are likely to contribute to the clinical NDI phenotype. Finally, our data highlight the involvement of the renin-angiotensin-aldosterone system in NDI pathophysiology and provide clues to explain the effectiveness of diuretics and indomethacin in the treatment of NDI.
Schliebe
Nicole
N
Institute of Biochemistry, Molecular Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
Strotmann
Rainer
R
Busse
Kathy
K
Mitschke
Doreen
D
Biebermann
Heike
H
Schomburg
Lutz
L
Köhrle
Josef
J
Bär
Jörg
J
Römpler
Holger
H
Wess
Jürgen
J
Schöneberg
Torsten
T
Sangkuhl
Katrin
K
D000818:Animals; D018500:Diabetes Insipidus, Nephrogenic / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D006706:Homeostasis / Q000502:physiology; D006955:Hypernatremia / Q000378:metabolism / Q000503:physiopathology; D007031:Hypothalamus / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D017483:Receptors, Vasopressin / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000502:physiology*
D017483:Receptors, Vasopressin; D000254:Sodium-Potassium-Exchanging ATPase