Abstract: Non-human animals and methods and compositions for making and using them are provided, wherein said non-human animals have a genome comprising an engineered or recombinant diversity cluster within an immunoglobulin heavy chain variable region, which engineered or recombinant diversity cluster comprises an insertion of one or more coding sequences of a non-immunoglobulin polypeptide of interest. Non-human animals described herein express antibodies characterized by complementary determining regions (CDRs), in particular, CDR3s having diversity that directs binding to particular antigens. Methods for producing antibodies from non-human animals are also provided, which antibodies contain human variable regions and mouse constant regions.

Abstract: Methods and compositions are provided for generating antigen-binding proteins against a foreign antigen of interest.

Abstract: Methods and compositions are provided for making one or more targeted genetic modifications at a target genomic locus within a cell and for producing non-human animals comprising the modified genomic locus. The methods employ two or more large targeting vectors which are capable of recombining with each other and with the target genomic locus in a single genomic targeting step. The methods may also be employed in combination with a nuclease agent. Methods and compositions are also provided for enhancing homologous recombination at a target genomic locus in a cell. The methods employ two or more nucleic acids comprising one or more overlapping sequences. The methods may be employed in combination with a nuclease agent or without a nuclease agent.

Abstract: Disclosed herein are genetically modified rodent animals comprising in their genome a nucleic acid which comprises a nucleotide sequence encoding a human CR1 polypeptide, wherein the rodent animals display a human-like expression of the human CR1 polypeptide. Also disclosed herein are isolated rodent cells including rodent embryonic stem cells, and rodent tissues. Further disclosed are nucleic acid vectors and methods for making the genetically modified rodent animals, as well as methods of using such genetically modified rodent animals for screening and testing candidate compounds.

Abstract: Mice having a restricted immunoglobulin heavy chain locus are provided, wherein the locus is characterized by a single polymorphic human VH gene segment, a plurality of human DH gene segments and a plurality of JH gene segments. Methods for making antibody sequences that bind an antigen (e.g., a viral antigen) are provided, comprising immunizing a mouse with an antigen of interest, wherein the mouse comprises a single human VH gene segment, a plurality of human DH gene segments and a plurality of JH gene segments, at the endogenous immunoglobulin heavy chain locus.

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: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion in an immunoglobulin constant region CH1 gene (optionally a deletion in a hinge region) of an IgG, IgA, IgD, and/or IgE, and wherein the mouse is capable of expressing a functional IgM. Genetically modified mice are described, including mice having a functional IgM gene and modified to have a deletion of a CH1 domain and a hinge region in a heavy chain constant domain that is not an IgM, e.g., in an IgG heavy chain constant domain. Genetically modified mice that make human variable/mouse constant chimeric heavy chain antibodies (antibodies that lack a light chain), fully mouse heavy chain antibodies, or fully human heavy chain antibodies are provided.

Abstract: Genetically modified non-human animals are provided that express an immunoglobulin variable domain that comprises at least one histidine, wherein the at least one histidine is encoded by a substitution of a non-histidine codon in the germline of the animal with a histidine codon, or the insertion of a histidine codon in a germline immunoglobulin nucleic acid sequence. Immunoglobulin genes comprising histidines in one or more CDRs, in an N-terminal region, and/or in a loop 4 region are also provided. Immunoglobulin variable domains comprising one or more histidines (e.g., histidine clusters) substituted for non-antigen-binding non-histidine residues. Non-human animals that are progeny of animals comprising modified heavy chain variable loci (V, D, J segments), modified light chain variable loci (V, J segments), and rearranged germline light chain genes (VJ sequences) are also provided. Non-human animals that make immunoglobulin domains that bind antigens in a pH-sensitive manner are provided.

Abstract: The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I and MHC II polypeptides and/or human or humanized ?2 microglobulin polypeptide, 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: 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: A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses a single light chain variable domain derived from a single rearranged light chain variable region gene in the germline of the non-human animal, wherein the single rearranged light chain variable region gene comprises a substitution of at least one non-histidine encoding codon with a histidine encoding codon. Methods of making non-human animals that express antibodies comprising a histidine-containing universal light chain are provided.

Abstract: Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a rodent (e.g., a mouse), wherein the non-human animals rearrange human immunoglobulin light chain gene segments in the context of heavy chain constant regions and express immunoglobulin-like molecules comprising human immunoglobulin light chain variable domains fused to heavy chain constant domains that are cognate with human immunoglobulin light chain variable domains fused to light chain constant domains.

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: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise an immunoglobulin heavy chain locus that includes unrearranged human immunoglobulin light chain gene segments and an immunoglobulin light chain locus that includes a single rearranged human light chain variable region nucleotide sequence. The unrearranged human light chain gene segments may be operably linked to a heavy chain constant region nucleotide sequence and the rearranged human immunoglobulin light chain variable region nucleotide sequence may be operably linked to a light chain constant region nucleotide sequence. Also provided are methods for obtaining nucleic acid sequences that encode immunoglobulin light chain variable domains capable of binding an antigen in the absence of a cognate variable domain, and expressing such nucleic acid sequences in a host cell, e.g., to generate a multispecific antigen-binding protein.

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: Non-human animals (and/or non-human cells) and methods of using the same are provided, which non-human animals (and/or non-human cells) have a genome comprising human antibody-encoding sequences (i.e., immunoglobulin genes). Non-human animals described herein express antibodies that contain immunoglobulin (Ig) light chains characterized by the presence of human V? domains. Non-human animals provided herein are, in some embodiments, characterized by expression of antibodies that contain human V? light chains that are encoded by human Ig? light chain-encoding sequences inserted into an endogenous Ig? light chain locus of said non-human animals Methods for producing antibodies from non-human animals are also provided, which antibodies contain human variable regions and mouse constant regions.

Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized B-cell activating factor gene. Non-human animals and cells that express a human or humanized B-cell activating factor protein from an endogenous B-cell activating factor locus are described.

Abstract: A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that present a choice of two human light chain variable gene segments such that the immunoglobulin light chains expresses by the mouse comprise one of the two human light chain variable gene segments. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided.

Abstract: Non-human animals (and/or non-human cells) and methods of using the same are provided, which non-human animals (and/or non-human cells) have a genome comprising human antibody-encoding sequences (i.e., immunoglobulin genes). Non-human animals described herein express antibodies that contain immunoglobulin (Ig) light chains characterized by the presence of human V? domains. Non-human animals provided herein are, in some embodiments, characterized by expression of antibodies that contain human V? light chains that are encoded by human Ig? light chain-encoding sequences inserted into an endogenous Ig? light chain locus of said non-human animals. Methods for producing antibodies from non-human animals are also provided, which antibodies contain human variable regions and mouse constant regions.