Generation and characterization of sodium-dicarboxylate cotransporter-deficient mice

H. T.B. Ho, Chi Bun Ko, A. K.H. Cheung, A. K.M. Lam, S. Tam, S. K. Chung, S. S.M. Chung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

23 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)63-71
Number of pages9
JournalKidney International
Volume72
Issue number1
DOIs
Publication statusPublished - 1 Jul 2007
Externally publishedYes

Keywords

  • Caloric restriction
  • Dicarboxylates
  • Gene knockout mice
  • NaDC1
  • Renal ischemia
  • Renal transporter

ASJC Scopus subject areas

  • Nephrology

Cite this