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Standardized,systemic phenotypic analysis reveals kidney dysfunction as main alteration of Kctd1 I27N mutant mice
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نویسنده
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kumar s. ,rathkolb b. ,sabrautzki s. ,krebs s. ,kemter e. ,becker l. ,beckers j. ,bekeredjian r. ,brommage r. ,calzada-wack j. ,garrett l. ,hölter s.m. ,horsch m. ,klingenspor m. ,klopstock t. ,moreth k. ,neff f. ,rozman j. ,fuchs h. ,gailus-durner v. ,hrabe de angelis m. ,wolf e. ,aigner b.
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منبع
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journal of biomedical science - 2017 - دوره : 24 - شماره : 1
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چکیده
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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. © 2017 the author(s).
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کلیدواژه
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Animal model; Kctd1; SEN syndrome; Systematic phenotype analysis
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آدرس
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chr. for molecular animal breeding and biotechnology,laboratory for functional genome analysis,gene center,lmu munich,munich,81377, Germany, chr. for molecular animal breeding and biotechnology,laboratory for functional genome analysis,gene center,lmu munich,munich,81377,germany,german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,member of german center for diabetes research (dzd),neuherberg,85764, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,research unit comparative medicine,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764, Germany, chr. for molecular animal breeding and biotechnology,laboratory for functional genome analysis,gene center,lmu munich,munich,81377, Germany, chr. for molecular animal breeding and biotechnology,laboratory for functional genome analysis,gene center,lmu munich,munich,81377, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,department of neurology,friedrich-baur-institute,university hospital munich,munich,80336, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,member of german center for diabetes research (dzd),neuherberg,85764,germany,chr. of experimental genetics,center of life and food sciences weihenstephan,tu munich,freising-weihenstephan,85350, Germany, department of medicine iii,division of cardiology,university of heidelberg,heidelberg,69120, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,institute of pathology,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,institute of developmental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,institute of developmental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,member of german center for diabetes research (dzd),neuherberg,85764, Germany, molecular nutritional medicine,else kröner-fresenius center,tu munich,freising-weihenstephan,85350, Germany, department of neurology,friedrich-baur-institute,university hospital munich,munich,80336,germany,german center for vertigo and balance disorders,university hospital munich,munich,81377,germany,munich cluster for systems neurology (synergy),munich,80336,germany,german center for neurodegenerative diseases (dzne),munich,80336, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,member of german center for diabetes research (dzd),neuherberg,85764, Germany, institute of pathology,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,member of german center for diabetes research (dzd),neuherberg,85764,germany,molecular nutritional medicine,else kröner-fresenius center,tu munich,freising-weihenstephan,85350, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,member of german center for diabetes research (dzd),neuherberg,85764, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,member of german center for diabetes research (dzd),neuherberg,85764, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,85764,germany,member of german center for diabetes research (dzd),neuherberg,85764,germany,chr. of experimental genetics,center of life and food sciences weihenstephan,tu munich,freising-weihenstephan,85350,germany,german center for vertigo and balance disorders,university hospital munich,munich,81377, Germany, chr. for molecular animal breeding and biotechnology,laboratory for functional genome analysis,gene center,lmu munich,munich,81377, Germany, chr. for molecular animal breeding and biotechnology,laboratory for functional genome analysis,gene center,lmu munich,munich,81377, Germany
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