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Clinical chemistry of human FcRn transgenic mice

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Abstract

Mice genetically engineered to express human FcRn are valuable models for the evaluation of therapeutic antibodies in the context of human FcRn in vivo. However, only limited clinical chemistry information on these mouse strains is available. Thus, we have compared 30 clinical chemical parameters of C57BL/6J wild-type mice, murine FcRn-knockout mice, and two human FcRn transgenic mouse strains expressing human FcRn in the absence of murine FcRn. Since FcRn-mediated recycling prevents albumin and IgG from intracellular degradation, significant differences for both proteins were observed in the murine FcRn-knockout mice. Mice lacking FcRn show lower IgG and albumin levels compared to wild-type mice. The most prominent differences in clinical chemical parameters can be explained by secondary effects of the altered albumin levels of murine FcRn-knockout mice on liver metabolism, as similar tendencies have been observed in analbuminemic Nagase rats and hypoalbuminemic human patients, showing an overall increased liver metabolism. Both human FcRn transgenic strains show clinical chemical parameters similar to those found for wild-type mice, with the exception of endogenous IgG levels, which are greatly reduced in these mice.

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Acknowledgments

The German Mouse Clinic is supported by grants from the German Federal Ministry of Education and Research (NGFNplus: 01GS0850, 01GS0851) and the European Union (EUMODIC LSHG-2006-037188). We thank Elfi Holupirek and Andreas Wolfert for excellent technical support in serum analyses.

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Authors and Affiliations

  1. Roche Diagnostics GmbH, Pharma Research and Early Development, Nonnenwald 2, 82377, Penzberg, Germany

    Carsten Stein & Lothar Kling

  2. The Jackson Laboratory, Bar Harbor, ME, 04609, USA

    Gabriele Proetzel & Derry C. Roopenian

  3. Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Zentrum München, 85764, Oberschleißheim, Germany

    Martin Hrabě de Angelis & Birgit Rathkolb

  4. Institute of Molecular Animal Breeding and Biotechnology, Ludwig-Maximilians-Universität, 81377, München, Germany

    Carsten Stein, Eckhard Wolf & Birgit Rathkolb

  5. Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technical University Munich, 85350, Freising-Weihenstephan, Germany

    Martin Hrabě de Angelis

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  1. Carsten Stein
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  2. Lothar Kling
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Correspondence to Carsten Stein.

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Stein, C., Kling, L., Proetzel, G. et al. Clinical chemistry of human FcRn transgenic mice. Mamm Genome 23, 259–269 (2012). https://doi.org/10.1007/s00335-011-9379-6

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