Humanized mouse models of the FcRn recycling pathway
The present disclosure provides improved humanized IgG1 FCRN mouse models for use, for example, in estimating serum half-life of therapeutic proteins such as monoclonal antibodies.
1. A mouse comprising:
a nucleic acid encoding human neonatal Fc receptor (FCRN); and
a nucleic acid, or a set of nucleic acids, encoding a chimeric immunoglobulin that comprises a mouse light chain variable region, a mouse light chain constant region, a mouse heavy chain variable region, and a chimeric heavy chain constant region comprising the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7,
wherein the mouse comprises a null mutation in endogenous FcRn.
2. The mouse of claim 1 , wherein cells of the mouse express the human FCRN and the chimeric immunoglobulin.
3. The mouse of claim 1 , wherein the immunoglobulin comprises a human hinge sequence.
4. The mouse of claim 3 , wherein the human hinge sequence comprises the amino acid sequence of SEQ ID NO: 2.
5. The mouse of claim 1 , wherein the nucleic acid encoding the immunoglobulin comprises a sequence that has at least 90% identity to the sequence of SEQ ID NO: 1.