TY  - JOUR
A1  - Kumar, Sudhir
A1  - Rathkolb, Birgit
A1  - Sabrautzki, Sibylle
A1  - Krebs, Stefan
A1  - Kemter, Elisabeth
A1  - Becker, Lore
A1  - Beckers, Johannes
A1  - Bekeredjian, Raffi
A1  - Brommage, Robert
A1  - Calzada-Wack, Julia
A1  - Garrett, Lillian
A1  - Hölter, Sabine M.
A1  - Horsch, Marion
A1  - Klingenspor, Martin
A1  - Klopstock, Thomas
A1  - Moreth, Kristin
A1  - Neff, Frauke
A1  - Rozman, Jan
A1  - Fuchs, Helmut
A1  - Gailus-Durner, Valérie
A1  - Hrabe de Angelis, Martin
A1  - Wolf, Eckhard
A1  - Aigner, Bernhard
SP  - 1
Y1  - 2017///
TI  - Standardized, systemic phenotypic analysis reveals kidney dysfunction as main alteration of Kctd1  I27N mutant mice
SN  - 1423-0127
VL  - 24
ID  - heidok23363
PB  - BioMed Central
AV  - public
IS  - 57
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/23363/
JF  - Journal of Biomedical Science
N2  - Background: Increased levels of blood plasma urea were used as phenotypic parameter for establishing novel mouse models for kidney diseases on the genetic background of C3H inbred mice in the phenotype-driven Munich ENU mouse mutagenesis project. The phenotypically dominant mutant line HST014 was established and further analyzed.   Methods: Analysis of the causative mutation as well as the standardized, systemic phenotypic analysis of the mutant line was carried out.   Results: The causative mutation was detected in the potassium channel tetramerization domain containing 1 (Kctd1) gene which leads to the amino acid exchange Kctd1  I27N thereby affecting the functional BTB domain of the protein. This line is the first mouse model harboring a Kctd1 mutation. Kctd1  I27N homozygous mutant mice die perinatally. Standardized, systemic phenotypic analysis of Kctd1  I27N heterozygous mutants was carried out in the German Mouse Clinic (GMC). Systematic morphological investigation of the external physical appearance did not detect the specific alterations that are described in KCTD1 mutant human patients affected by the scalp-ear-nipple (SEN) syndrome. The main pathological phenotype of the Kctd1  I27N heterozygous mutant mice consists of kidney dysfunction and secondary effects thereof, without gross additional primary alterations in the other phenotypic parameters analyzed. Genome-wide transcriptome profiling analysis at the age of 4 months revealed about 100 differentially expressed genes (DEGs) in kidneys of Kctd1  I27N heterozygous mutants as compared to wild-type controls.   Conclusions: In summary, the main alteration of the Kctd1  I27N heterozygous mutants consists in kidney dysfunction. Additional analyses in 9?21 week-old heterozygous mutants revealed only few minor effects.
CY  - London
EP  - 12
ER  -