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Kemter, Elisabeth; Rathkolb, Birgit; Becker, Lore; Bolle, Ines; Busch, Dirk H.; Dalke, Claudia; Elvert, Ralf; Favor, Jack; Graw, Jochen; Hans, Wolfgang; Ivandic, Boris; Kalaydjiev, Svetoslav; Klopstock, Thomas; Rácz, Ildikó; Rozman, Jan; Schrewe, Anja; Schulz, Holger; Zimmer, Andreas; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabé de Angelis, Martin; Wolf, Eckhard and Aigner, Bernhard (2014): Standardized, systemic phenotypic analysis of Slc12a(1299F) mutant mice. In: Journal of Biomedical Science 21:68 [PDF, 493kB]


Background: Type I Bartter syndrome is a recessive human nephropathy caused by loss-of-function mutations in the SLC12A1 gene coding for the Na+-K+-2Cl(-) cotransporter NKCC2. We recently established the mutant mouse line Slc12a1(1299F) exhibiting kidney defects highly similar to the late onset manifestation of this hereditary human disease. Besides the kidney defects, low blood pressure and osteopenia were revealed in the homozygous mutant mice which were also described in humans. Beside its strong expression in the kidney, NKCC2 has been also shown to be expressed in other tissues in rodents ie. the gastrointestinal tract, pancreatic beta cells, and specific compartments of the ear, nasal tissue and eye. Results: To examine if, besides kidney defects, further organ systems and/or metabolic pathways are affected by the 0lc12oilL99r mutation as primary or secondary effects, we describe a standardized, systemic phenotypic analysis of the mutant mouse line Slc12a1(1299F) in the German Mouse Clinic. Slc-12a1(1299F) homozygous mutant mice and Sic12a1(1299F) heterozygous mutant littermates as controls were tested at the age of 4-6 months. Beside the already published changes in blood pressure and bone metabolism, a significantly lower body weight and fat content were found as new phenotypes for Slc12a1(1299F) homozygous mutant mice. Small additional effects included a mild erythropenic anemia in homozygous mutant males as well as a slight hyperalgesia in homozygous mutant females. For other functions, such as immunology, lung function and neurology, no distinct alterations were observed. Conclusions: In this systemic analysis no clear primary effects of the Slc12a1(1299F) mutation appeared for the organs other than the kidneys where Slc12a1 expression has been described. On the other hand, long-term effects additional and/or secondary to the kidney lesions might also appear in humans harboring SLC12A1 mutations.

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