title: Generation and Standardized, Systemic Phenotypic Analysis of Pou3f3L423P Mutant Mice.
abstract: 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 recessive mutant line HST011 was established and further analyzed. The causative mutation was detected in the POU domain, class 3 transcription factor 3 (Pou3f3) gene, which leads to the amino acid exchange Pou3f3L423P thereby affecting the conserved homeobox domain of the protein. Pou3f3 homozygous knockout mice are published and show perinatal death. Line Pou3f3L423P is a viable mouse model harboring a homozygous Pou3f3 mutation. Standardized, systemic phenotypic analysis of homozygous mutants was carried out in the German Mouse Clinic. Main phenotypic changes were low body weight and a state of low energy stores, kidney dysfunction and secondary effects thereof including low bone mineralization, multiple behavioral and neurological defects including locomotor, vestibular, auditory and nociceptive impairments, as well as multiple subtle changes in immunological parameters. Genome-wide transcriptome profiling analysis of kidney and brain of Pou3f3L423P homozygous mutants identified significantly regulated genes as compared to wild-type controls.
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, 81377, Munich, Germany.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, 81377, Munich, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, 81377, Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kemter
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.|Member of German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Sabrautzki
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
authors.forename: Dian
authors.initials: D
authors.lastname: Michel
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.|Institute of Medical Microbiology, Immunology, and Hygiene, TU Munich, 81675, Munich, Germany.
authors.forename: Thure
authors.initials: T
authors.lastname: Adler
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
authors.forename: Lore
authors.initials: L
authors.lastname: Becker
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.|Member of German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.|Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, TU Munich, 85350, Freising-Weihenstephan, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
authors.affiliation: Institute of Medical Microbiology, Immunology, and Hygiene, TU Munich, 81675, Munich, Germany.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
authors.forename: Lillian
authors.initials: L
authors.lastname: Garrett
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.|Member of German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hans
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Hölter
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Horsch
authors.affiliation: Molecular Nutritional Medicine, Else Kröner-Fresenius Center, TU Munich, 85350, Freising-Weihenstephan, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Klingenspor
authors.affiliation: Department of Neurology, Friedrich-Baur-Institut, LMU Munich, 80336, Munich, Germany.|German Center for Vertigo and Balance Disorders, University Hospital Munich, Campus Grosshadern, 81377, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klopstock
authors.affiliation: Laboratory of Molecular Neurobiology, Department of Psychiatry, University of Bonn, 53105, Bonn, Germany.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Rácz
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.|Member of German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.|Molecular Nutritional Medicine, Else Kröner-Fresenius Center, TU Munich, 85350, Freising-Weihenstephan, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rozman
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.|Department of Neurology, Friedrich-Baur-Institut, LMU Munich, 80336, Munich, Germany.|German Center for Vertigo and Balance Disorders, University Hospital Munich, Campus Grosshadern, 81377, Munich, Germany.
authors.forename: Ingrid Liliana
authors.initials: IL
authors.lastname: Vargas Panesso
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.|Department of Neurology, Friedrich-Baur-Institut, LMU Munich, 80336, Munich, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Vernaleken
authors.affiliation: Laboratory of Molecular Neurobiology, Department of Psychiatry, University of Bonn, 53105, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.|Member of German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.|Member of German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gailus-Durner
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.|Member of German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.|Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, TU Munich, 85350, Freising-Weihenstephan, Germany.|German Center for Vertigo and Balance Disorders, University Hospital Munich, Campus Grosshadern, 81377, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, 81377, Munich, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, 81377, Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Aigner
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D016678:Genome / Q000235:genetics; D006720:Homozygote; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D016296:Mutagenesis / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D050809:POU Domain Factors / Q000235:genetics*; D010641:Phenotype
chemical_list: D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; C074065:Pou3f3 protein, mouse