PMID- 21553221 OWN - NLM STAT- MEDLINE DCOM- 20120117 LR - 20211020 IS - 1432-1777 (Electronic) IS - 0938-8990 (Linking) VI - 22 IP - 9-10 DP - 2011 Oct TI - Generation of N-ethyl-N-nitrosourea-induced mouse mutants with deviations in hematological parameters. PG - 495-505 LID - 10.1007/s00335-011-9328-4 [doi] AB - 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. FAU - Aigner, Bernhard AU - Aigner B AD - 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, Oberschleibetaheim, Munich, Germany. b.aigner@gen.vetmed.uni-muenchen.de FAU - Rathkolb, Birgit AU - Rathkolb B FAU - Klempt, Martina AU - Klempt M FAU - Wagner, Sibylle AU - Wagner S FAU - Michel, Dian AU - Michel D FAU - Klaften, Matthias AU - Klaften M FAU - Laufs, Jurgen AU - Laufs J FAU - Schneider, Boris AU - Schneider B FAU - Sedlmeier, Reinhard AU - Sedlmeier R FAU - Hrabe de Angelis, Martin AU - Hrabe de Angelis M FAU - Wolf, Eckhard AU - Wolf E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110508 PL - United States TA - Mamm Genome JT - Mammalian genome : official journal of the International Mammalian Genome Society JID - 9100916 RN - 0 (Mutagens) RN - 0 (Receptors, Transferrin) RN - 0 (Tfrc protein, mouse) RN - P8M1T4190R (Ethylnitrosourea) SB - IM MH - Animals MH - Base Sequence MH - *Disease Models, Animal MH - Ethylnitrosourea MH - Female MH - Genetic Linkage MH - Genotype MH - Hematologic Diseases/*genetics MH - Hematologic Tests MH - Male MH - Mice/*genetics MH - Mice, Inbred C3H MH - Mice, Inbred C57BL MH - *Mutagenesis MH - Mutagens MH - *Mutation MH - Phenotype MH - Receptors, Transferrin/genetics MH - Reference Values EDAT- 2011/05/10 06:00 MHDA- 2012/01/18 06:00 CRDT- 2011/05/10 06:00 PHST- 2011/02/01 00:00 [received] PHST- 2011/04/14 00:00 [accepted] PHST- 2011/05/10 06:00 [entrez] PHST- 2011/05/10 06:00 [pubmed] PHST- 2012/01/18 06:00 [medline] AID - 10.1007/s00335-011-9328-4 [doi] PST - ppublish SO - Mamm Genome. 2011 Oct;22(9-10):495-505. doi: 10.1007/s00335-011-9328-4. Epub 2011 May 8.