Hyposulfatemia, growth retardation, reduced fertility, and seizures in mice lacking a functional NaSi-1 gene

AUTOR(ES)

Dawson, Paul A.

FONTE

National Academy of Sciences

RESUMO

Inorganic sulfate is required for numerous functions in mammalian physiology, and its circulating levels are proposed to be maintained by the Na+-SO42- cotransporter, (NaSi-1). To determine the role of NaSi-1 in sulfate homeostasis and the physiological consequences in its absence, we have generated a mouse lacking a functional NaSi-1 gene, Nas1. Serum sulfate concentration was reduced by >75% in Nas1-/- mice when compared with Nas1+/+ mice. Nas1-/- mice exhibit increased urinary sulfate excretion, reduced renal and intestinal Na+-SO42- cotransport, and a general growth retardation. Nas1-/- mouse body weight was reduced by >20% when compared with Nas1+/+ and Nas1+/- littermates at 2 weeks of age and remained so throughout adulthood. Nas1-/- females had a lowered fertility, with a 60% reduction in litter size. Spontaneous clonic seizures were observed in Nas1-/- mice from 8 months of age. These data demonstrate NaSi-1 is essential for maintaining sulfate homeostasis, and its expression is necessary for a wide range of physiological functions.

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