Table 2.

Overview of phenotypes of genetically modified mouse models targeting WNK kinases or associated proteins

Mouse ModelPhenotypeReference
Salt-sensitive hypotensive models
    NKCC2−/− (indomethacin rescued)Bartter-like54
    SORLA−/−Bartter-like37
    NCC−/−Gitelman-like56
    transgenic (WNK4WT)Gitelman-like63
    “hypomorphic” WNK4Gitelman-like64
    SPAK−/−Gitelman-like66
    SPAK243A/243A (kinase-dead knockin)Gitelman-like67
    SGK−/−Salt-sensitive hypotension, hyperkalemia60
Salt-sensitive hypertensive models
    transgenic (WNK4PHAII)FHHt-like63
    WNK4D561A/+ (knockin)FHHt-like70
No phenotype
    transgenic (NCC)No phenotype71
    KS-WNK1−/−No phenotype73
    collecting duct–specific ENaC−/−No phenotype59
  • See text for abbreviations of protein names and explanations of the phenotypes. FHHt, familial hyperkalemic hypertension.