The
anion exchanger SAT-1 [
sulfate anion transporter 1 (Slc26a1)] is considered an important regulator of
oxalate and
sulfate homeostasis, but the mechanistic basis of these critical roles remain undetermined. Previously, characterization of the SAT-1-knockout (KO) mouse suggested that the loss of SAT-1-mediated
oxalate secretion by the intestine was responsible for the
hyperoxaluria, hyperoxalemia, and
calcium oxalate urolithiasis reportedly displayed by this model. To test this hypothesis, we compared the transepithelial fluxes of 14C-oxalate, 35SO42- , and 36Cl- across isolated, short-circuited segments of the distal ileum, cecum, and distal colon from wild-type (WT) and SAT-1-KO mice. The absence of SAT-1 did not impact the transport of these
anions by any part of the intestine examined. Additionally, SAT-1-KO mice were neither hyperoxaluric nor hyperoxalemic. Instead, 24-h urinary
oxalate excretion was almost 50% lower than in WT mice. With no contribution from the intestine, we suggest that this may reflect the loss of SAT-1-mediated
oxalate efflux from the liver. SAT-1-KO mice were, however, profoundly hyposulfatemic, even though there were no changes to intestinal
sulfate handling, and the renal clearances of
sulfate and
creatinine indicated diminished rates of
sulfate reabsorption by the proximal tubule. Aside from this distinct
sulfate phenotype, we were unable to reproduce the
hyperoxaluria, hyperoxalemia, and
urolithiasis of the original SAT-1-KO model. In conclusion,
oxalate and
sulfate transport by the intestine were not dependent on SAT-1, and we found no evidence supporting the long-standing hypothesis that intestinal SAT-1 contributes to
oxalate and
sulfate homeostasis. NEW & NOTEWORTHY SAT-1 is a membrane-bound
transport protein expressed in the intestine, liver, and kidney, where it is widely considered essential for the excretion of
oxalate, a potentially toxic waste metabolite. Previously,
calcium oxalate kidney stone formation by the SAT-1-knockout mouse generated the hypothesis that SAT-1 has a major role in
oxalate excretion via the intestine. We definitively tested this proposal and found no evidence for SAT-1 as an intestinal
anion transporter contributing to
oxalate homeostasis.