Mice expressing humanized Fc α receptors
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsJohn McWhirter, Naxin Tu, Andrew J. Murphy, Lynn MacDonald
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AssigneeRegeneron Pharmaceuticals, Inc.
InventorsJohn McWhirter, Naxin Tu, Andrew J. Murphy, Lynn MacDonald
Estimating the term…
Provided herein are methods and compositions related to mice that express human or humanized Foot receptors (FcaR) from an FcaR locus positioned in the mouse leukocyte receptor complex (LRC). In certain embodiments, such mice are useful for in vivo testing of therapeutic agents comprising a human IgA Fc (e.g., the testing of the pharmacokinetic and/or pharmacodynamic properties of such therapeutic agents and dosing regimens). Also provided herein are methods of using such mice, cells from such mice, methods of making such mice, and ES cells comprising the same genetic modifications as such mice. Provided herein are methods and compositions related to mice that express human or humanized Foot receptors (FcaR) from an FcaR locus positioned in the mouse leukocyte receptor complex (LRC). In certain embodiments, such mice are useful for in vivo testing of therapeutic agents comprising a human IgA Fc (e.g., the testing of the pharmacokinetic and/or pharmacodynamic properties of such therapeutic agents and dosing regimens). Also provided herein are methods of using such mice, cells from such mice, methods of making such mice, and ES cells comprising the same genetic modifications as such mice.
A mouse comprising in its genome an Fc alpha receptor (FcαR) locus positioned in the mouse leukocyte receptor complex (LRC), wherein the FcαR locus comprises a nucleic acid sequence encoding a FcαR polypeptide comprising a human extracellular domain and a human or rodent cytoplasmic domain, and further comprising in its genome a human or humanized Fc gamma receptor (FcγR) locus, a human or humanized IgH locus, a human or humanized Igκ locus, a human or humanized Igλ locus, a human or humanized FcRn locus, a human or humanized β2M locus, and/or a human or humanized FcεR1α locus.
A mouse comprising in its genome an Fc alpha receptor (FcαR) locus positioned in the mouse leukocyte receptor complex (LRC), wherein the FcαR locus comprises a nucleic acid sequence encoding a FcαR polypeptide comprising a human extracellular domain, a human transmembrane domain, and a human cytoplasmic domain, wherein the FcαR locus comprises human exons 1-5 of the human Fc alpha receptor gene, and wherein the FcαR locus further comprises a nucleic acid sequence present in the 5′UTR of the human NCR1 gene.
A mouse comprising in its genome an Fc alpha receptor (FcαR) locus positioned in the mouse leukocyte receptor complex (LRC), wherein the FcαR locus comprises a nucleic acid sequence encoding a FcαR polypeptide comprising a human extracellular domain, a rodent transmembrane domain, and a rodent cytoplasmic domain, wherein the FcαR locus comprises a non-coding portion of non-mouse rodent FcαR exon 1, a coding portion of human FcαR exons 1 and 2, human FcαR exons 3 and 4, and non-mouse rodent FcαR exon 5.
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