We floxed exon 2 of the mouse BSND locus by heterologous recombination. Constitutive knockout mice obtained by crossing these mice to deleter mice showed severe growth retardation and early mortality in the first postnatal days. Barttin knockout mice were characterized by severe salt and fluid loss as expected from humans with mutations in barttin. When we looked for ClC-K in the kidneys of these mice, immunoreactivity was absent except for weak intracellular staining, consistent with barttin's established role in trafficking ClC-K channels to the surface. This also applied to the thin limb of HENLE, where predominantly ClC-K1 is expressed. Although this channel trafficks to the surface without barttin in Xenopus oocytes, barttin seems to be necessary for stability and surface expression in the kidney. As early mortality precluded detailed urine analysis, we also generated a cre knock-in in the Tamm-Horsfall-locus (to be described elsewhere), which allowed partial, but not complete, deletion of barttin in the thick ascending limb of HENLE's loop. Tamm-Horsfall-cre/barttin mice grew to adulthood, but showed increased urine volume, severe salt loss and increased salt appetite. Current work focuses on the inner ear phenotype of conditional barttin knockout mice.