title: Standardized, systemic phenotypic analysis reveals kidney dysfunction as main alteration of Kctd1  I27N mutant mice
creator: Kumar, Sudhir
creator: Rathkolb, Birgit
creator: Sabrautzki, Sibylle
creator: Krebs, Stefan
creator: Kemter, Elisabeth
creator: Becker, Lore
creator: Beckers, Johannes
creator: Bekeredjian, Raffi
creator: Brommage, Robert
creator: Calzada-Wack, Julia
creator: Garrett, Lillian
creator: Hölter, Sabine M.
creator: Horsch, Marion
creator: Klingenspor, Martin
creator: Klopstock, Thomas
creator: Moreth, Kristin
creator: Neff, Frauke
creator: Rozman, Jan
creator: Fuchs, Helmut
creator: Gailus-Durner, Valérie
creator: Hrabe de Angelis, Martin
creator: Wolf, Eckhard
creator: Aigner, Bernhard
subject: ddc-610
subject: 610 Medical sciences Medicine
description: 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.
publisher: BioMed Central
date: 2017
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/23363/1/12929_2017_Article_365.pdf
identifier: DOI:
identifier: urn:nbn:de:bsz:16-heidok-233636
identifier:   Kumar, Sudhir ; Rathkolb, Birgit ; Sabrautzki, Sibylle ; Krebs, Stefan ; Kemter, Elisabeth ; Becker, Lore ; Beckers, Johannes ; Bekeredjian, Raffi ; Brommage, Robert ; Calzada-Wack, Julia ; Garrett, Lillian ; Hölter, Sabine M. ; Horsch, Marion ; Klingenspor, Martin ; Klopstock, Thomas ; Moreth, Kristin ; Neff, Frauke ; Rozman, Jan ; Fuchs, Helmut ; Gailus-Durner, Valérie ; Hrabe de Angelis, Martin ; Wolf, Eckhard ; Aigner, Bernhard  (2017) Standardized, systemic phenotypic analysis reveals kidney dysfunction as main alteration of Kctd1 I27N mutant mice.  Journal of Biomedical Science, 24 (57).  pp. 1-12.  ISSN 1423-0127     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/23363/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng