Tubule function in transgenic mice.
Many transporters involved in renal electrolyte transport have recently been identified and cloned. The availability of genetically manipulated mice, especially transgenic knockout and overexpression models, has made it possible to examine ion transport in kidney tubules in the absence of specific transporters whose function in defined tubule segments is well known. Such selective alterations in transport functions are also useful to investigate adaptive mechanisms by which the kidney compensates for specific transport lesions. Examples of mouse models displaying altered renal transport function include targeted disruption of genes encoding the Na-H exchanger isoforms NHE2 and NHE3, the thiazide-sensitive Na-Cl cotransporter TSC, CFTR, and the colonic isoform of the H,K-ATPase. Moreover, mice with null mutation in the Na-H exchanger isoform NHE1 have been also identified. In addition, a strain of mice with enhanced H,K-ATPase expression due to a defective endocytosis signal has been developed. Other transporter knockout models will soon become available. In this review we focus on the physiological characterization of renal tubule transport in animals with well-defined genetic transport lesions.
Wang
T
T
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520-8026, USA. Tong.Wang@yale.edu
Giebisch
G
G
D000804:Angiotensin II / Q000235:genetics / Q000502:physiology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D017136:Ion Transport / Q000235:genetics; D007684:Kidney Tubules / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D049992:Sodium Chloride Symporters; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism; D027981:Symporters
D002352:Carrier Proteins; D015222:Sodium Channels; D049992:Sodium Chloride Symporters; D017923:Sodium-Hydrogen Exchangers; D027981:Symporters; D000804:Angiotensin II; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D019001:Nitric Oxide Synthase; D017506:H(+)-K(+)-Exchanging ATPase