Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR/Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric OX40, and methods of use thereof.

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric (e.g., humanized) Lymphocyte Activation Gene 3 (LAG-3), and methods of use thereof.

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric OX40, and methods of use thereof.

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric TIGIT (e.g., humanized TIGIT), and methods of use thereof.

Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR/Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD137, and methods of use thereof.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD28, and methods of use thereof.

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric TIGIT (e.g., humanized TIGIT), and methods of use thereof.

This disclosure provides a rodent model of prostate cancer. The rodents disclosed herein comprise a transgene that provides prostate-specific expression of an oncogenic protein (e.g, an SV40 tumor antigen) under the control of 5 and 3 regulatory regions of a mouse probasin gene. The rodents develop progressive forms of prostate tumor that resemble the development of human prostate cancer.