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.

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.

The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.

Non-human animals comprising a human or humanized IL-4 and/or IL-4Rα nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4Rα gene with a human IL-4 gene and/or IL-4Rα gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4Rα gene under control of non-human IL-4Rα regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4Rα-encoding sequence with human or humanized IL-4Rα-encoding sequence at an endogenous non-human C IL-4Rα locus. Non-human animals comprising human or humanized IL-4 gene and/or IL-4Rα sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

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.

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 β2 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.

The present invention provides a novel modified protein which is to be used, as a novel detection tool relating to gene expression, for detecting a chromatin open structure more easily at a higher sensitivity than by the conventional technique. The present invention relates to: a nucleic acid binding fluorescent protein, said protein containing a DNA binding domain in which 3 or more TAL-repeats are repeatedly connected, characterized by binding independently from base sequences; and a method for fluorescent labeling of an open chromatin in a vital cell, said method comprising a step for transferring a gene encoding a nucleic acid binding protein into the vital cell, characterized in that the nucleic acid binding protein is a protein comprising a DNA binding domain, in which 3 or more TAL-repeats are repeatedly connected, and a fluorescent protein directly or indirectly bound thereto and the DNA binding domain binds to a nucleic acid independently from base sequences.

The disclosure provides immunogenic cells expressing LMP1, and use thereof in activating T cells and treating cancer. Also provided are methods of producing the immunogenic cells.

The present invention relates to a hemophilia B rat and a method of producing the hemophilia B rat. More particularly, the present invention relates to a hemophilia B rat having F9 factor knocked-down or knocked-out and a method of producing the hemophilia B rat.

An object of the present invention is to provide a humanized mouse in which human hematopoietic stem cells can be engrafted for a long term. The present invention relates to a humanized rodent having human neutrophils circulating in a periphery, obtained by transplanting a human hematopoietic stem cell into a human G-CSF gene knock-in rodent, which is an immunodeficient rodent deficient in a G-CSF receptor function by knock-in of a human G-CSF gene at a G-CSF receptor locus, wherein a human G-CSF is expressed and a rodent G-CSF receptor is not expressed.