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

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: The present disclosure provides, among other things, genetically modified non-human animals whose germline genome comprises an engineered endogenous immunoglobulin ? light chain locus comprising a single rearranged human immunoglobulin ? light chain variable region operably linked to a non-human C? gene segment, where the single rearranged human immunoglobulin ? light chain variable region comprises a human V? gene segment and a human J? gene segment. All immunoglobulin ? light chains expressed by B cells of the genetically modified non-human animal include human immunoglobulin ? light chain variable domains expressed from the single rearranged human immunoglobulin ? light chain variable region or a somatically hypermutated version thereof. Such animals, tissues from such animals, and cells from such animals represent an effective platform for producing antibodies, e.g., bispecific antibodies.

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: A method of obtaining a nucleotide sequence, from an immunized genetically modified non-human mammal, encoding an immunoglobulin variable domain of an antibody specific for a particular antigen is disclosed. A method for making antibodies against a particular antigen is also disclosed.

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 (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 and methods and compositions for making and using them are provided, which 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 DH segments that are each operably linked to a 23-mer recombination signal sequence. Methods for producing antibodies from non-human animals are also provided, which antibodies optionally contain human variable regions and rodent, e.g., constant regions.

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

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

Abstract: Non-human animals (and/or non-human cells) and methods of using and making 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 human Ig? light chains, in whole or in part. In particular, non-human animals provided herein are, in some embodiments, characterized by expression of antibodies that contain human Ig? light chains, in whole or in part, 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.

Abstract: A non-human animal (e.g., a rodent) model for diseases associated with a C9ORF72 heterologous hexanucleotide repeat expansion sequence is provided, which non-human animal comprises a heterologous hexanucleotide repeat (GGGGCC) in an endogenous C9ORF72 locus. A non-human animal disclosed herein comprising a heterologous hexanucleotide repeat expansion sequence comprising at least one instance, e.g., repeat, of a hexanucleotide (GGGGCC) sequence may further exhibit a characteristic and/or phenotype associated with one or more neurodegenerative disorders (e.g., amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD), etc.). Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)) are also provided.

Abstract: Non-human animals (and/or non-human cells) and methods of using and making 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 human Ig? light chains, in whole or in part. In particular, non-human animals provided herein are, in some embodiments, characterized by expression of antibodies that contain human Ig? light chains, in whole or in part, 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.

Abstract: Non-human animals and methods and compositions for making and using them are provided, which 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 DH segments that are each operably linked to a 23-mer recombination signal sequence. Methods for producing antibodies from non-human animals are also provided, which antibodies optionally contain human variable regions and rodent, e.g., constant regions.

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 (and/or non-human cells) and methods of using and making 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 human Ig? light chains, in whole or in part. In particular, non-human animals provided herein are, in some embodiments, characterized by expression of antibodies that contain human Ig? light chains, in whole or in part, 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.

Abstract: A non-human animal (e.g., a rodent) model for diseases associated with a C9ORF72 heterologous hexanucleotide repeat expansion sequence is provided, which non-human animal comprises a heterologous hexanucleotide repeat (GGGGCC) in an endogenous C9ORF72 locus. A non-human animal disclosed herein comprising a heterologous hexanucleotide repeat expansion sequence comprising at least one instance, e.g., repeat, of a hexanucleotide (GGGGCC) sequence may further exhibit a characteristic and/or phenotype associated with one or more neurodegenerative disorders (e.g., amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD), etc.). Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)) are also provided.

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