Sodium transport deficiency and sodium balance in gene-targeted mice.
Animals with induced or natural null mutations in renal NaCl and water transporter genes provide a powerful tool to study the physiological mechanisms that enable the kidney to optimize the match between glomerular filtration rate and tubular reabsorption. Deficiencies in the Na/H exchanger NHE3 and in the water channel aquaporin 1 (AQP1) cause reductions in proximal fluid absorption which are accompanied by proportionate decrements in glomerular filtration rate (GFR). Compensation of the transport defect by a reduction in filtered load is so efficient that clinically symptomatic Na losses are not observed in either NHE3 or AQP1 deficient animals. On the other hand, severe syndromes of salt wasting are caused by loss of function of the Na,K,2Cl-cotransporter (NKCC2) in the thick ascending limb, or of the epithelial Na channel (ENaC) the collecting duct indicating that the severity of Na dysregulation is unrelated to the basal absorption of NaCl in a given nephron segment. In these states, the increased delivery of Na to downstream segments is not monitored by a sensor linked to the site of filtrate formation. In the absence of adaptations in the filtered load intrarenal compensation of a circumscribed NaCl malabsorption by adjustment of NaCl transport in other nephron segments is sometimes insufficient, particularly in the immature kidney of the newborn.
Schnermann
J
J
NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
D000818:Animals; D001477:Bartter Syndrome / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011546:Pseudohypoaldosteronism / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics* / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics* / Q000378:metabolism
D015222:Sodium Channels; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D012964:Sodium