Over-expression of the bovine FcRn in the mammary gland results in increased IgG levels in both milk and serum of transgenic mice

• Published in: Immunology Vol. 122; no. 3; pp. 401 - 408
• Main Authors: Lu, Wei, Zhao, Zhihui, Zhao, Yaofeng, Yu, Shuyang, Zhao, Yiqiang, Fan, Baoliang, Kacskovics, Imre, Hammarström, Lennart, Li, Ning
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.11.2007; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Animals; Cattle; Female; Gene Expression Regulation - immunology; Genetic Vectors; Half-Life; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - metabolism; Mammary Glands, Animal - immunology; Medicin och hälsovetenskap; Mice; Mice, Transgenic; Milk - immunology; neonatal Fc receptor; Original; Receptors, Fc - genetics; Receptors, Fc - immunology; RNA, Messenger - genetics; Tissue Distribution; Transgenes; transgenic mice
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2007.02654.x

The neonatal Fc receptor (FcRn) protects immunoglobulin G (IgG) from catabolism and is also responsible for IgG absorption in the neonatal small intestine. However, whether it mediates the transfer of IgG from plasma to milk still remains speculative. In the present study, we have generated transgenic mice that over-express the bovine FcRn (bFcRn) in their lactating mammary glands. Significantly increased IgG levels were observed in the sera and milk from transgenic animals, suggesting that the over-expressed bFcRn could bind and protect endogenous mouse IgG and thus extend its lifespan. We also found that injected human IgG showed a significantly longer half-life (7-8 days) in the transgenic mice than in controls (2·9 days). Altogether, the data suggested that bFcRn could bind both mouse and human IgG, showing a cross-species FcRn-IgG binding activity. However, we found no selective accumulation of endogenous mouse IgG or injected bovine IgG in the milk of the transgenic females, supporting a previous hypothesis that IgG was transported from serum to milk in an inverse correlation to its binding affinity to FcRn.