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Generation of N-ethyl-N-nitrosourea-induced mouse mutants with deviations in hematological parameters

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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.

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Acknowledgments

This work was supported by the German Human Genome Project (DHGP) and the National Genome Research Network (NGFN) (MHdA, EW).

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The authors have no conflicts of interest, financial or otherwise, to declare.

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Authors and Affiliations

  1. 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

    Bernhard Aigner, Birgit Rathkolb, Martina Klempt & Eckhard Wolf

  2. Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, and Chair for Experimental Genetics, TU Munich, Freising-Weihenstephan, Helmholtz Zentrum München, Neuherberg, Germany

    Sibylle Wagner, Dian Michel, Matthias Klaften & Martin Hrabé de Angelis

  3. Ingenium Pharmaceuticals, Martinsried, Germany

    Jürgen Laufs, Boris Schneider & Reinhard Sedlmeier

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  1. Bernhard Aigner
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  2. Birgit Rathkolb
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  3. Martina Klempt
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  4. Sibylle Wagner
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  5. Dian Michel
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  6. Matthias Klaften
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  7. Jürgen Laufs
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  8. Boris Schneider
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  9. Reinhard Sedlmeier
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  10. Martin Hrabé de Angelis
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  11. Eckhard Wolf
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Correspondence to Bernhard Aigner.

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Aigner, B., Rathkolb, B., Klempt, M. et al. Generation of N-ethyl-N-nitrosourea-induced mouse mutants with deviations in hematological parameters. Mamm Genome 22, 495–505 (2011). https://doi.org/10.1007/s00335-011-9328-4

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