Standardized, systemic phenotypic analysis reveals kidney dysfunction as main alteration of Kctd1 I27N mutant mice
Abstract 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 HST01...
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2017-08-01
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Series: | Journal of Biomedical Science |
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Online Access: | http://link.springer.com/article/10.1186/s12929-017-0365-5 |
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doaj-743f0c22d5854380b4885e06f531eb0e |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sudhir Kumar Birgit Rathkolb Sibylle Sabrautzki Stefan Krebs Elisabeth Kemter Lore Becker Johannes Beckers Raffi Bekeredjian Robert Brommage Julia Calzada-Wack Lillian Garrett Sabine M. Hölter Marion Horsch Martin Klingenspor Thomas Klopstock Kristin Moreth Frauke Neff Jan Rozman Helmut Fuchs Valérie Gailus-Durner Martin Hrabe de Angelis Eckhard Wolf Bernhard Aigner |
spellingShingle |
Sudhir Kumar Birgit Rathkolb Sibylle Sabrautzki Stefan Krebs Elisabeth Kemter Lore Becker Johannes Beckers Raffi Bekeredjian Robert Brommage Julia Calzada-Wack Lillian Garrett Sabine M. Hölter Marion Horsch Martin Klingenspor Thomas Klopstock Kristin Moreth Frauke Neff Jan Rozman Helmut Fuchs Valérie Gailus-Durner Martin Hrabe de Angelis Eckhard Wolf Bernhard Aigner Standardized, systemic phenotypic analysis reveals kidney dysfunction as main alteration of Kctd1 I27N mutant mice Journal of Biomedical Science Animal model Kctd1 SEN syndrome Systematic phenotype analysis |
author_facet |
Sudhir Kumar Birgit Rathkolb Sibylle Sabrautzki Stefan Krebs Elisabeth Kemter Lore Becker Johannes Beckers Raffi Bekeredjian Robert Brommage Julia Calzada-Wack Lillian Garrett Sabine M. Hölter Marion Horsch Martin Klingenspor Thomas Klopstock Kristin Moreth Frauke Neff Jan Rozman Helmut Fuchs Valérie Gailus-Durner Martin Hrabe de Angelis Eckhard Wolf Bernhard Aigner |
author_sort |
Sudhir Kumar |
title |
Standardized, systemic phenotypic analysis reveals kidney dysfunction as main alteration of Kctd1 I27N mutant mice |
title_short |
Standardized, systemic phenotypic analysis reveals kidney dysfunction as main alteration of Kctd1 I27N mutant mice |
title_full |
Standardized, systemic phenotypic analysis reveals kidney dysfunction as main alteration of Kctd1 I27N mutant mice |
title_fullStr |
Standardized, systemic phenotypic analysis reveals kidney dysfunction as main alteration of Kctd1 I27N mutant mice |
title_full_unstemmed |
Standardized, systemic phenotypic analysis reveals kidney dysfunction as main alteration of Kctd1 I27N mutant mice |
title_sort |
standardized, systemic phenotypic analysis reveals kidney dysfunction as main alteration of kctd1 i27n mutant mice |
publisher |
BMC |
series |
Journal of Biomedical Science |
issn |
1423-0127 |
publishDate |
2017-08-01 |
description |
Abstract 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. |
topic |
Animal model Kctd1 SEN syndrome Systematic phenotype analysis |
url |
http://link.springer.com/article/10.1186/s12929-017-0365-5 |
work_keys_str_mv |
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doaj-743f0c22d5854380b4885e06f531eb0e2020-11-25T01:31:18ZengBMCJournal of Biomedical Science1423-01272017-08-0124111210.1186/s12929-017-0365-5Standardized, systemic phenotypic analysis reveals kidney dysfunction as main alteration of Kctd1 I27N mutant miceSudhir Kumar0Birgit Rathkolb1Sibylle Sabrautzki2Stefan Krebs3Elisabeth Kemter4Lore Becker5Johannes Beckers6Raffi Bekeredjian7Robert Brommage8Julia Calzada-Wack9Lillian Garrett10Sabine M. Hölter11Marion Horsch12Martin Klingenspor13Thomas Klopstock14Kristin Moreth15Frauke Neff16Jan Rozman17Helmut Fuchs18Valérie Gailus-Durner19Martin Hrabe de Angelis20Eckhard Wolf21Bernhard Aigner22Chair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis, Gene Center, LMU MunichChair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis, Gene Center, LMU MunichGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthChair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis, Gene Center, LMU MunichChair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis, Gene Center, LMU MunichGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthDepartment of Medicine III, Division of Cardiology, University of HeidelbergGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthMolecular Nutritional Medicine, Else Kröner-Fresenius Center, TU MunichDepartment of Neurology, Friedrich-Baur-Institute, University Hospital MunichGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthInstitute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental HealthGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthGerman Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental HealthChair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis, Gene Center, LMU MunichChair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis, Gene Center, LMU MunichAbstract 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.http://link.springer.com/article/10.1186/s12929-017-0365-5Animal modelKctd1SEN syndromeSystematic phenotype analysis |