Generation and characterization of sodium-dicarboxylate cotransporter-deficient mice.
The sodium-dependent dicarboxylate cotransporter (NaDC1) has a proposed function of reabsorbing various Krebs cycle intermediates in the kidney and the small intestine. Since Krebs cycle intermediates have been suggested to be important for renal cell survival and recovery after hypoxia and reoxygenation, the transporter may play a role in the recovery of the kidney. Additionally, mutations in the transporter homolog in Drosophila led to fly longevity which was thought to be similar to that induced by caloric restriction (CR). To clarify the role of the sodium dicarboxylate cotransporter in vivo we generated cotransporter-deficient mice. These knockout mice excreted significantly higher amounts of various Krebs cycle intermediates in their urine; thus confirming the proposed function to reabsorb these metabolic intermediates in the kidney. No other phenotypic change was identified in these mice, however. Transporter deficiency did not affect renal function under normal physiological conditions, nor did it have an effect on renal damage and recovery from ischemic injury. Additionally, the absence of the transporter did not lead to metabolic or physiological changes associated with CR. Our results suggest that although the sodium dicarboxylate cotransporter is involved in regulating levels of various Krebs cycle intermediates in the kidney, impaired uptake of these intermediates does not significantly affect renal function under normal or ischemic stress.
Ho
H T B
HT
Department of Physiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Ko
B C B
BC
Cheung
A K H
AK
Lam
A K M
AK
Tam
S
S
Chung
S K
SK
Chung
S S M
SS
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D031204:Caloric Restriction; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002951:Citrates / Q000097:blood; D002952:Citric Acid Cycle / Q000502:physiology*; D003404:Creatinine / Q000097:blood; D029382:Dicarboxylic Acid Transporters / Q000235:genetics* / Q000502:physiology*; D007668:Kidney / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics* / Q000502:physiology*; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D027981:Symporters / Q000235:genetics* / Q000502:physiology*
D002951:Citrates; D029382:Dicarboxylic Acid Transporters; D029363:Organic Anion Transporters, Sodium-Dependent; C490479:Slc13a2 protein, mouse; D027981:Symporters; D003404:Creatinine