Hyposulfatemia, growth retardation, reduced fertility, and seizures in mice lacking a functional NaSi-1 gene.
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.
School of Biomedical Sciences, University of Queensland, Brisbane 4072, Australia.
Paul A
PA
Dawson
Laurent
L
Beck
Daniel
D
Markovich
D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood; D001692:Biological Transport; D015139:Blotting, Southern; D001835:Body Weight; D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D005298:Fertility; D005822:Genetic Vectors; D006130:Growth Disorders / Q000209:etiology; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D012313:RNA / Q000378:metabolism; D012640:Seizures / Q000209:etiology; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates / Q000097:blood / Q000652:urine; D015238:Sulfotransferases / Q000378:metabolism; D027981:Symporters / Q000235:genetics* / Q000502:physiology*; D013997:Time Factors
D001647:Bile Acids and Salts; D027682:Cation Transport Proteins; D018076:DNA, Complementary; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates; D027981:Symporters; D012313:RNA; D015238:Sulfotransferases