Abstract: Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats) genetically engineered to express a humanized or human T cell receptor (TCR) comprising a variable domain encoded by (a) at least one human TCR variable region ? gene segment and a (human) TCR ? constant region gene sequence and/or (b) or at least one human TCR variable region ? gene segment and a (human) TCR ? constant region gene sequence. Also provided are embryos, tissues, and cells expressing the same. Methods for making a genetically engineered animal that expresses the humanized or human ? and/or ? TCR are also provided. Methods for using the genetically engineered animals that mount a substantially humanized T cell immune response for developing human therapeutics are also provided.

Abstract: Provided herein are genetically modified cells and genetically modified non-human animals (e.g., rats and mice) comprising: (i) a Rag1 and/or Rag2 gene knock-out; (ii) a IL2rg gene knock-out; and (iii) a homozygous null mutation in the non-human animal Heme oxygenase-1 (Hmox-1) gene, and optionally a Fah gene knock-out and/or expressing one or more human or humanized polypeptides. Methods and compositions of making and using such genetically modified cells and non-human animals are also provided.

Abstract: 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.

Abstract: Provided herein are methods and compositions related to the in vivo testing of therapeutic agents comprising a human Fc in genetically modified rodents (e.g., the testing of the pharmacokinetic and/or pharmacodynamic properties of such a therapeutic agent in genetically modified rodents). In some embodiments the genetically modified rodents express antibodies comprising a human Fc (e.g., a human IgG1 Fc, a human IgG4 Fc). In some embodiments, the rodents express fully human antibodies (i.e., antibodies having human heavy chains and human light (? or ?) chains). In certain embodiments the genetically modified rodents comprise one or more Fc receptors with a human extracellular domain (e.g., a Neonatal Fc Receptor (FcRn), a ?-2-microglobulin polypeptide (?2M), a Fc ? receptor 1 ? (Fc?R1?), a Fc ? receptor 1 alpha (Fc?R1a), a Fc gamma receptor 2a (Fc?R2a), a Fc gamma receptor 2b (Fc?R2b), a Fc gamma receptor 3a (Fc?R3a), a Fc gamma receptor 3b (Fc?R3b), a Fc gamma receptor 2c (Fc?R2c)).

Abstract: Genetically modified mice and methods and compositions for making and using the same are provided, wherein the genetic modification comprises humanization of an Fc?RI protein.

Abstract: Disclosed herein are rodents (such as, but not limited to, mice and rats) genetically modified to comprise a humanized Cxcl13 gene. The rodents disclosed herein have been shown to support better engraftment and proliferation of human cells such as chronic lymphocytic leukemic cells. Compositions and methods for making such genetically modified rodents, as well as methods of using such genetically modified rodents for testing candidate therapeutic agents (e.g., candidate anti-cancer drugs), are provided.

Abstract: Provided herein are methods and compositions related to the in vivo testing of therapeutic agents comprising a human Fc in genetically modified rodents (e.g., the testing of the pharmacokinetic and/or pharmacodynamic properties of such a therapeutic agent in genetically modified rodents). In some embodiments the genetically modified rodents express antibodies comprising a human Fc (e.g., a human IgG1 Fc, a human IgG4 Fc). In some embodiments, the rodents express fully human antibodies (i.e., antibodies having human heavy chains and human light (? or ?) chains). In certain embodiments the genetically modified rodents comprise one or more Fc receptors with a human extracellular domain (e.g., a Neonatal Fc Receptor (FcRn), a ?-2-microglobulin polypeptide (?2M), a Fc ? receptor 1? (Fc?R1?), a Fc ? receptor 1 alpha (Fc?R1a), a Fc gamma receptor 2a (Fc?R2a), a Fc gamma receptor 2b (Fc?R2b), a Fc gamma receptor 3a (Fc?R3a), a Fc gamma receptor 3b (Fc?R3b), a Fc gamma receptor 2c (Fc?R2c)).

Abstract: The invention provides a genetically modified non-human animal that comprises in its genome unrearranged T cell receptor variable gene loci, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified non-human animal and methods of making the same. Various methods of using the genetically modified non-human animal are also provided.

Abstract: The invention provides a genetically modified non-human animal that comprises in its genome unrearranged T cell receptor variable gene loci, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified non-human animal and methods of making the same. Various methods of using the genetically modified non-human animal are also provided.

Abstract: Genetically modified mice and methods and compositions for making and using the same are provided, wherein the genetic modification comprises humanization of an Fc?RI protein.

Abstract: Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats) genetically engineered to express a humanized T cell co-receptor (e.g., humanized CD4 and/or CD8 (e.g., CD8? and/or CD8?)), a human or humanized T cell receptor (TCR) comprising a variable domain encoded by at least one human TCR variable region gene segment and/or a human or humanized major histocompatibility complex that binds the humanized T cell co-receptor (e.g., human or humanized MHC II (e.g., MHC II ? and/or MHC II ? chains) and/or MHC I (e.g., MHC I?) respectively, and optionally human or humanized ?2 microglobulin). Also provided are embryos, tissues, and cells expressing the same. Methods for making a genetically engineered animal that expresses at least one humanized T cell co-receptor (e.g., humanized CD4 and/or CD8), at least one humanized MHC that associates with the humanized T cell co-receptor (e.g., humanized MHC II and/or MHC I, respectively) and/or the humanized TCR are also provided.

Abstract: Disclosed herein are nucleic acids encoding for and proteins expressing chimeric C1q polypeptides, non-human animals comprising said nucleic acids, and methods of making or using said non-human animals.

Abstract: The invention provides genetically modified non-human animals that express a humanized MHC II protein (humanized MHC II ? and ? polypeptides), as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

Abstract: Disclosed herein are nucleic acids encoding for and proteins expressing chimeric C1q polypeptides, non-human animals comprising said nucleic acids, and methods of making or using said non-human animals.

Abstract: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity Fc?R locus, and wherein the mouse is capable of expressing a functional FcR?-chain. Genetically modified mice are described, including mice that express low affinity human Fc?R genes from the endogenous Fc?R locus, and wherein the mice comprise a functional FcR?-chain. Genetically modified mice that express up to five low affinity human Fc?R genes on accessory cells of the host immune system are provided.

Abstract: The invention provides genetically modified non-human animals that express a humanized MHC II protein (humanized MHC II ? and ? polypeptides), as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

Abstract: Provided herein are methods and compositions related to non-human animals that express exogenous Terminal Deoxynucleotidyltransferase (TdT).

Abstract: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity Fc?R locus, and wherein the mouse is capable of expressing a functional FcR?-chain. Genetically modified mice are described, including mice that express low affinity human Fc?R genes from the endogenous Fc?R locus, and wherein the mice comprise a functional FcR?-chain. Genetically modified mice that express up to five low affinity human Fc?R genes on accessory cells of the host immune system are provided.

Abstract: The invention provides genetically modified non-human animals that express a humanized MHC II protein (humanized MHC II ? and ? polypeptides), as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

Abstract: Provided herein are methods and compositions related to non-human animals that express exogenous Terminal Deoxynucleotidyltransferase (TdT).