title: Screen for alterations of iron related parameters in N-ethyl-N-nitrosourea-treated mice identified mutant lines with increased plasma ferritin levels.
abstract: Iron is essential for numerous cellular processes. For diagnostic purposes iron-related parameters in patients are assessed by clinical chemical blood analysis including the analysis of ferritin, transferrin and iron levels. Here, we retrospectively evaluated the use of these parameters in the phenotype-driven Munich N-ethyl-N-nitrosourea mouse mutagenesis project for the generation of novel animal models for human diseases. The clinical chemical blood analysis was carried out on more than 10,700 G1 and G3 offspring of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to deviations in the plasma levels of iron-related plasma parameters. We identified animals consistently exhibiting altered plasma ferritin or transferrin values. Transmission of the phenotypic deviations to the subsequent generations led to the successful establishment of three mutant lines with increased plasma ferritin levels. For two of these lines the causative mutations were identified in the Fth1gene and the Ireb2 gene, respectively. Thus, novel mouse models for the functional analysis of iron homeostasis were established by a phenotype-driven screen for mutant mice.
authors: Chair for Molecular Animal Breeding and Biotechnology, Department of Veterinary Sciences, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Feodor-Lynen-Str. 25, 81377, Munich, Germany, birgit.rathkolb@helmholtz-muenchen.de.
authors: Birgit
authors: B
authors: Rathkolb
authors: Martina
authors: M
authors: Klempt
authors: Sibylle
authors: S
authors: Sabrautzki
authors: Dian
authors: D
authors: Michel
authors: Matthias
authors: M
authors: Klaften
authors: Jürgen
authors: J
authors: Laufs
authors: Reinhard
authors: R
authors: Sedlmeier
authors: Wolfgang
authors: W
authors: Hans
authors: Helmut
authors: H
authors: Fuchs
authors: Martina U
authors: MU
authors: Muckenthaler
authors: Marion
authors: M
authors: Horsch
authors: Dean R
authors: DR
authors: Campagna
authors: Mark
authors: M
authors: Fleming
authors: Martin
authors: M
authors: Hrabé de Angelis
authors: Eckhard
authors: E
authors: Wolf
authors: Bernhard
authors: B
authors: Aigner
mesh_terms: D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005038:Ethylnitrosourea / Q000494:pharmacology*; D005260:Female; D005293:Ferritins / Q000097:blood*; D015870:Gene Expression; D056726:Genetic Association Studies; D008040:Genetic Linkage; D005820:Genetic Testing; D007501:Iron / Q000097:blood; D008297:Male; D008809:Mice, Inbred C3H; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology*; D010641:Phenotype; D014168:Transferrin / Q000378:metabolism
chemical_list: D009153:Mutagens; D014168:Transferrin; D005293:Ferritins; D007501:Iron; D005038:Ethylnitrosourea