title: Generation of N-ethyl-N-nitrosourea-induced mouse mutants with deviations in hematological parameters.
abstract: Research on hematological disorders relies on suitable animal models. We retrospectively evaluated the use of the hematological parameters hematocrit (HCT), hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell count (RBC), white blood cell count (WBC), and platelet count (PLT) in the phenotype-driven Munich N-ethyl-N-nitrosourea (ENU) mouse mutagenesis project as parameters for the generation of novel animal models for human diseases. The analysis was carried out on more than 16,000 G1 and G3 offspring of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to deviations in the levels of the chosen parameters. Identification of animals exhibiting altered values and transmission of the phenotypic deviations to the subsequent generations led to the successful establishment of mutant lines for the parameters MCV, RBC, and PLT. Analysis of the causative mutation was started in selected lines, thereby revealing a novel mutation in the transferrin receptor gene (Tfrc) in one line. Thus, novel phenotype-driven mouse models were established to analyze the genetic components of hematological disorders.
authors.affiliation: Department of Veterinary Sciences, Chair for Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Moorversuchsgut, Hackerstr. 27, 85764, Oberschleiβheim, Munich, Germany. b.aigner@gen.vetmed.uni-muenchen.de
authors.forename: Bernhard
authors.initials: B
authors.lastname: Aigner
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
authors.forename: Martina
authors.initials: M
authors.lastname: Klempt
authors.forename: Sibylle
authors.initials: S
authors.lastname: Wagner
authors.forename: Dian
authors.initials: D
authors.lastname: Michel
authors.forename: Matthias
authors.initials: M
authors.lastname: Klaften
authors.forename: Jürgen
authors.initials: J
authors.lastname: Laufs
authors.forename: Boris
authors.initials: B
authors.lastname: Schneider
authors.forename: Reinhard
authors.initials: R
authors.lastname: Sedlmeier
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabé de Angelis
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
mesh_terms: D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D005038:Ethylnitrosourea; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006402:Hematologic Diseases / Q000235:genetics*; D006403:Hematologic Tests; D008297:Male; D051379:Mice / Q000235:genetics*; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D009153:Mutagens; D009154:Mutation; D010641:Phenotype; D011990:Receptors, Transferrin / Q000235:genetics; D012016:Reference Values
chemical_list: D009153:Mutagens; D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse; D005038:Ethylnitrosourea