Clinical chemistry of human FcRn transgenic mice

• Published in: Mammalian genome Vol. 23; no. 3-4; pp. 259 - 269
• Main Authors: Stein, Carsten, Kling, Lothar, Proetzel, Gabriele, Roopenian, Derry C., de Angelis, Martin Hrabě, Wolf, Eckhard, Rathkolb, Birgit
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01-04-2012; Springer Nature B.V
• Subjects: Albumin; Albumins - metabolism; Animal Genetics and Genomics; Animals; Biomedical and Life Sciences; Cell Biology; Female; Genetic engineering; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; Human Genetics; Humans; Immunoglobulin G; Immunoglobulin G - blood; Life Sciences; Liver; Male; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic - blood; Receptors, Fc - genetics; Receptors, Fc - metabolism; Recycling; Transgenic mice; High Uric Acid Level; Uric Acid; Creatine Kinase; Total Calcium Level; Clinical Chemical Parameter
• ISSN: 0938-8990; 1432-1777
• DOI: 10.1007/s00335-011-9379-6

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.