SLC12A3 and Hypokalemia: In addition, homozygous knockout mice, which completely lack SPAK expression, display hypokalemia, hypomagnesemia, and hypocalciuria (Gitelman-like syndrome) and impaired vasoconstriction.19 Finally, mice expressing a mutated SPAK, which cannot be activated by WNK isoforms, show decreased phosphorylation and expression of NKCC2 and NCC, and significantly lower, salt-dependent BP.20 On a lifelong basis, even subtle genetic changes leading to mild sodium and water accumulation may cause a significant alteration in sodium and water balance, fluid retention, and subsequent chronic hypertension.21