Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.

Non-human animals, expressing humanized CD3 proteins are provided. Non-human animals, e.g., rodents, genetically modified to comprise in their genome humanized CD3 proteins are also provided. Additionally, provided are methods and compositions of making such non-human animals, as well as methods of using said non-human animals.

The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

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

A mouse artificial chromosome vector is stable in rodent cells, tissues, and/or individuals, specifically a mouse artificial chromosome vector derived from a mouse chromosome selected from mouse chromosome 10 and mouse chromosome 16. A cell or a non-human animal may include the vector. The vector may be used for producing proteins and human antibodies.

The present disclosure relates to an aglycosylated antibody-producing transgenic mouse and the use of an aglycosylated antibody produced therefrom. When the transgenic mouse of the present disclosure is used, it is possible to easily produce aglycosylated antibodies against various target antigens, and to precisely diagnose disease by detecting a glycoprotein biomarker using the produced aglycosylated antibody.

Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

The invention discloses methods for the generation of chimaeric humannon-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises (a) a deletion in an immunoglobulin constant region C.sub.H1 gene (optionally a deletion in a hinge region) of a heavy chain constant region gene sequence, and (b) replacement of one or all endogenous V.sub.H, D.sub.H and J.sub.H gene segments with at least one unrearranged light chain variable (V.sub.L) gene segment and at least one unrearranged light chain joining (J.sub.L) gene segment capable of recombining to form a rearranged light chain variable region (V.sub.L/J.sub.L) nucleotide sequence operably linked to the heavy chain constant region gene sequence comprising a deletion in the C.sub.H1 gene and/or insertion of a genetically engineered single rearranged light chain, wherein the mouse is capable of expressing a functional IgM, single domain antigen binding proteins, e.g., V.sub.L-single domain binding proteins, and a genetically engineered rearranged light chain.

Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.