title: Clinical chemistry of human FcRn transgenic mice.
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.
authors.affiliation: Roche Diagnostics GmbH, Pharma Research and Early Development, Nonnenwald 2, 82377, Penzberg, Germany. carsten.stein.cs1@roche.com
authors.forename: Carsten
authors.initials: C
authors.lastname: Stein
authors.forename: Lothar
authors.initials: L
authors.lastname: Kling
authors.forename: Gabriele
authors.initials: G
authors.lastname: Proetzel
authors.forename: Derry C
authors.initials: DC
authors.lastname: Roopenian
authors.forename: Martin Hrabě
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic / Q000097:blood*; D011961:Receptors, Fc / Q000235:genetics* / Q000378:metabolism
chemical_list: D000418:Albumins; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; C100688:Fc receptor, neonatal