Abstract: The present disclosure provides, in some aspects, humanized immunodeficient mouse models that support long-term engraftment and function of human T cells, natural killer cells, and myeloid cells, without the need for conditioning.

Abstract: A method of identifying anti-tumor activity of a test substance is provided along with a genetically-modified, immunodeficient mouse and methods of use, wherein the genetically-modified, immunodeficient mouse enables in vivo investigation of the interactions between the human immune system and human cancer.

Abstract: Provided herein, in some aspects, is a NOD.Cg-Prkdcscid Il2rgtm1Wj1/SzJ (NOD scid gamma or NSG™) mouse comprising a nucleic acid encoding human FLT3L and an inactivated mouse Flt3 allele, methods of producing the mouse, and methods of using the mouse.

Abstract: A method of identifying anti-tumor activity of a test substance is provided along with a genetically-modified, immunodeficient mouse and methods of use, wherein the genetically-modified, immunodeficient mouse enables in vivo investigation of the interactions between the human immune system and human cancer.

Abstract: Provided herein, in some aspects, is a NOD.Cg-Prkdcscid Il2rgtm1wjl/SzJ (NOD scid gamma or NSG™) mouse comprising a nucleic acid encoding human FLT3L and an inactivated mouse Flt3 allele, methods of producing the mouse, and methods of using the mouse.

Abstract: The present disclosure provides, in some aspects, an immunodeficient NOD-Fcgr1null mouse that may be used to measure human IgG antibody pharmacokinetics and activity, produce human IgG antibodies, and model human disease treatment.

Abstract: The present disclosure provides, in some aspects, a humanized immunodeficient mouse model of human fibrosis. A humanized immunodeficient mouse model provided herein may be used, for example, for modeling human fibrosis, predicting human fibrosis, and testing putative fibrosis treatments.

Abstract: This invention provides, as a therapeutic method for eradication of neoplastic diseases of the blood with poor diagnosis, a cell co-expressing a chimeric antigen receptor (CAR) protein and a CXCL12 receptor protein on the cell membrane, and an agent and a pharmaceutical composition having anti-tumor activity, which comprises such cell.

Abstract: The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/B1N, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2retmlWjl/SzJ (NSG), NOD.Cg-Rag1tm1Mom Il2rgtmlWjl/SzJ (NRG) and NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice.

Abstract: A NOD.Cg-PrkdcscidH2rgtm1 Wjl/SzJ.(NOD-scid-IL2r?null, NSG) mouse which is genetically modified such that the en NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present, invention. According to specific aspects the genetically modified NSG mouse, is a NOD.Cg-PrkdcscidH2-K1tml Bpe H2-Ab1eml Mvw H2-D1tml Bpe H2rgtm Wjl/SzJ (NSG-Kb Db)null(IAnull)) mouse, NSG-RIP-DTR (Kb Db)null(IAnull) mouse, or a NOD.Cg-B2mtmlUnePrKdcscidH2dlAb1-E?H2rgtm1 Wjl/SzJ (NSG-B2Mnull(IA IEnull)) mouse. Human, immune cells and/or human: tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice.

Abstract: The present disclosure provides an immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG™) mouse models that comprise an inactivated mouse Flt3 allele, a nucleic acid encoding human interleukin 3 (IL3), a nucleic acid encoding human granulocyte/macrophage-stimulating factor (GM-CSF), a nucleic acid encoding human stem cell factor (SCF), and a HLA-A2/H2-D/B2M transgene encoding (i) a human B2-microglubulin (B2M) covalently linked to MHC class 1, alpha 1, and alpha2 binding domains of a human HLA-A2.1 gene and (ii) alpha3 cytoplasmic and transmembrane domains of murine H2-db.

Abstract: The present disclosure provides a transgenic, immunocompromised mouse engineered to express a human angiotensin converting enzyme 2 (huACE2) sequence. The huACE2 sequence may be operably linked to a human keratin 18 (hKRT18) promoter or the endogenous mouse angiotensin converting enzyme 2 (mACE2) promoter. Transgenic immunocompromised mice of the present disclosure may be utilized in methods of evaluating a test agent for reducing or preventing SARS-CoV-2 infection.

Abstract: Provided herein, in some aspects, is a NOD.Cg-Prkdcscid Il2rgtm1wjl/SzJ (NOD scid gamma or NSG™) mouse comprising a nucleic acid encoding human FLT3L and an inactivated mouse Flt3 allele, methods of producing the mouse, and methods of using the mouse.

Abstract: The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/B1N, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2retmlWjl/SzJ (NSG), NOD.Cg-Rag1tm1Mom Il2rgtmlWjl/SzJ (NRG) and NOD.Cg-Prkdcscid Il2rgtm1Sug/JicTac (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice.

Abstract: An immunodeficient mouse is provided which is useful as a model of functions and regulation of human natural killer (NK) cells and other interleukin 15 (IL-15)-dependent cell populations and processes in studies of human immunity, cancer, infectious diseases, and other areas. According to specific aspects, an immunodeficient mouse is provided which is genetically modified to express human interleukin 15, wherein the mouse does not have or produce functional mouse natural killer cells, and wherein the mouse is modified to include human natural killer cells. Methods of identifying anti-tumor activity of a test substance using a mouse of the present invention are described along with methods of making the mouse.

Abstract: The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/BIN, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ (NSG), NOD.Cg-Rag1tm1Mom IL2rgtm1Wjl/SzJ (NRG) and NOD.Cg-Prkdcscid IL2rgtm1Sug/JicTAc (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice.

Abstract: A NOD.Cg-PrkdcscidH2rgtm1 Wjl/SzJ.(NOD-scid-IL2r?null, NSG) mouse which is genetically modified such that the en NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present, invention. According to specific aspects the genetically modified NSG mouse, is a NOD.Cg-PrkdcscidH2-K1tml Bpe H2-Ab1eml Mvw H2-D1tml Bpe H2rgtm Wjl/SzJ (NSG-Kb Db)null(IAnull)) mouse, NSG-RIP-DTR (Kb Db)null(IAnull) mouse, or a NOD.Cg-B2mtmlUnePrKdcscidH2dlAb1-E?H2rgtm1 Wjl/SzJ (NSG-B2Mnull(IA IEnull)) mouse. Human, immune cells and/or human: tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice.

Abstract: A genetically-modified, immunodeficient mouse is provided along with methods of use, wherein the mouse includes (a) a nucleotide sequence encoding human stem cell factor (hSCF); (b) a nucleotide sequence encoding human granulocyte-macrophage colony-stimulating factor (hGM-CSF); (c) a nucleotide sequence encoding human interleukin-3 (hIL-3); and (d) a nucleotide sequence encoding human colony-stimulating factor 1 (hCSF1), wherein each of the nucleotide sequences is operably linked to a promoter, and wherein the genetically-modified, immunodeficient mouse expresses hSCF, hGM-CSF, hIL-3, and hCSF1, wherein the genetically-modified, immunodeficient mouse allows engraftment of human hematopoietic stem cells along with engraftment of human-patient derived tumor xenografts and/or human tumor cell lines to enable in vivo investigation of the interactions between the human immune system and human cancer.

Abstract: One or more embodiments of the present invention include an immunodeficient mouse genetically modified to include a gene encoding a PiZ variant (Glu342Lys) of human ?-1 antitrypsin (AAT), wherein the mouse expresses the PiZ variant of human ?-1 antitrypsin (Z-AAT), and has a reduced number of mouse hepatocytes compared to an immunodeficient mouse of the same type which does not express Z-AAT. The immunodeficient mouse genetically modified to include a gene encoding a PiZ variant of human AAT can be a genetically modified NSG, NRG or NOG mouse. The immunodeficient mouse may further include xenogeneic hepatocytes, such as human hepatocytes. Putative treatments of human liver disease can be assessed in mice provided according to aspects of the present disclosure.

Abstract: A genetically modified immunodeficient non-human animal whose genome includes a genetic modification that renders the non-human animal deficient in macrophages and/or macrophage anti-human red blood cell activity so as to prolong the survival of human red blood cells when administered into said non-human animal is provided according to aspects of the present invention. Methods of assaying effects of putative therapeutic agents in such a genetically modified immunodeficient non-human animal are provided by the present invention.