Functional and molecular characterization of a peritoneal dialysis model in the C57BL/6J mouse.
BACKGROUND
Animal models are important for understanding the physiology and pathophysiology of peritoneal transport during peritoneal dialysis (PD). Mechanistic investigations of rat and rabbit models of PD are mostly based on intervention studies using pharmacologic agents or blocking antibodies. These models may be limited by the time-course, lack of specificity, or side effects of such interventions. Genetically modified mice could provide an attractive alternative to the above models. In this study, we have characterized PD parameters and tested the effect of gender and dialysate volume and/or osmolality in the C57BL/6J mouse.


METHODS
Mice were submitted to a 2-hour peritoneal equilibration test in order to obtain permeability parameters. The expression of the water channel aquaporin-1 (AQP1) and endothelial NO synthase (eNOS) was investigated at the protein (immunoblotting, immunostaining) and mRNA [real-time reverse-transcription-polymerase chain reaction (RT-PCR)] levels. The potential effect of gender on these parameters was also studied.


RESULTS
Exposure of mice to 2 mL of 3.86% glucose dialysate yielded equilibration curves for urea and glucose, a sodium sieving, and a net ultrafiltration (UF) that were remarkably similar to those obtained in rats. The increase in dialysate volume (from 2 mL to 3 mL and 6 mL) resulted in a higher ultrafiltration and, for the highest volume, an increase in the diffusive mass transport coefficient (MTAC) for urea. The increase in dialysate glucose concentration (from 1.36% to 3.86% and 7%) resulted in increased sodium sieving and higher UF, whereas the MTAC for urea was unchanged. In comparison with males, females had a similar peritoneal transport rate for small solutes but a significantly lower sodium sieving, reflecting a lower AQP1 mRNA and protein expression in the peritoneum.


CONCLUSIONS
These data demonstrate the structural and functional similarity between mouse and rat models of PD, and further emphasize the relevance of mouse models to understand PD in humans. They also suggest that gender may influence water transport and AQP1 expression in the peritoneum.
Ni
Jie
J
Division of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium.
Cnops
Yvette
Y
Debaix
Huguette
H
Boisdé
Isabelle
I
Verbavatz
Jean-Marc
JM
Devuyst
Olivier
O
D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001693:Biological Transport, Active; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012727:Sex Characteristics; D013045:Species Specificity; D014882:Water-Electrolyte Balance
C496021:Aqp1 protein, mouse; C496022:Aqp1 protein, rat; D020346:Aquaporins; D018076:DNA, Complementary; D012333:RNA, Messenger; D051398:Aquaporin 1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C496316:Nos3 protein, rat