Galphaq-dependent signaling cascades stimulate water-seeking behavior.
We used the mouse nephrin promoter to express a constitutively active Galphaq [Galphaq(Q>L)] transgene in mice. As previously reported, the transgene was expressed in kidney, pancreas, and brain, and the kidney phenotype was characterized by albuminuria and reduced nephron mass. Additional studies revealed a second phenotype characterized by polyuria and polydipsia. The polyuric phenotype was not caused by abnormal glucose metabolism or hypercalcemia but was accompanied by reduced urinary concentrating ability. Additional studies found that 1) water restriction was associated with an appropriate increase in serum vasopressin levels in transgenic (TG) mice; 2) the urinary concentrating defect was not corrected by administration of desamino-d-arginine vasopressin (DDAVP); and 3) papillary length was similar in TG and non-TG mice. To examine the renal response to DDAVP at the molecular level, we monitored aquaporin 2 (AQP2) and vasopressin V2 receptor (V2R) mRNA levels in mouse kidney. Consistent with the known effects of vasopressin, administration of DDAVP caused a decrease in V2R mRNA levels and an increase in AQP2 mRNA levels in both TG and non-TG animals, suggesting an appropriate renal response to DDAVP in the TG mice. To determine whether the urine concentrating abnormality was the result of primary polydipsia, water intake by TG mice was restricted to the amount ingested by non-TG animals. After 5 days, urinary concentrating ability was similar in TG mice and non-TG littermate controls. These data are consistent with the notion that expression of the Galphaq(Q>L) transgene in the brain induced primary polydipsia in the TG mice.
Wang
Liming
L
Division of Nephrology, Department of Medicine, Duke University, Durham, NC 27710, USA.
Flannery
Patrick J
PJ
Athirakul
Krairerk
K
Dunn
Stephen R
SR
Kourany
Wissam M
WM
Spurney
Robert F
RF
D000821:Animal Feed; D000818:Animals; D017931:DNA Primers; D004231:Diuresis; D004327:Drinking Behavior; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D012016:Reference Values; D015398:Signal Transduction; D013599:Systole; D014667:Vasopressins / Q000097:blood; D014867:Water
D017931:DNA Primers; D014867:Water; D014667:Vasopressins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11