Hyposulfatemia, growth retardation, reduced fertility, and seizures in mice lacking a functional NaSi-1 gene
Hyposulfatemia, growth retardation, reduced fertility, and seizures in mice lacking a functional NaSi-1 gene
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DOI：
10.1073/pnas.2231298100
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发表时间：
2003-11-11
影响因子：
11.1
通讯作者：
Markovich, D
中科院分区：
文献类型：
--
作者：
Dawson, PA;Beck, L;Markovich, D
无机硫酸盐是哺乳动物生理学中许多功能所必需的，其循环水平被认为是由Na+-SO 42-协同转运蛋白（NaSi-1）维持的。为了确定NaSi-1在硫酸盐稳态中的作用以及在其缺失的情况下的生理后果，我们产生了缺乏功能性NaSi-1基因Nas 1的小鼠。与Nas 1（+/+）小鼠相比，Nas 1（-/-）小鼠的血清硫酸盐浓度降低>75%。Nas 1（-/-）小鼠表现出尿硫酸盐排泄增加，肾脏和肠道Na+-SO 42-共转运减少，以及全身生长迟缓。与Nas 1（+/+）和Nas 1（+/-）同窝出生的小鼠相比，Nas 1（-/-）小鼠体重在2周龄时降低>20%，并且在整个成年期保持如此。Nas 1（-/-）雌性的生育力降低，窝仔数减少60%。从8月龄开始，在Nas 1（-/-）小鼠中观察到自发性阵挛发作。这些数据表明NaSi-1是维持硫酸盐稳态所必需的，并且其表达对于广泛的生理功能是必需的。
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.