Provided herein, in some aspects, is a NOD.Cg-Prkdc.sup.scid Il2rg.sup.tm1wjl/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.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) CD47, and methods of use thereof.

The present disclosure provides nucleic acid expression cassettes, vectors, compositions and methods for the treatment of ATPase-mediated diseases in a subject.

The invention is concerned with a fusion protein comprising interleukin 13 and a regulatory cytokine, for example, an interleukin chosen from interleukin 4, interleukin 10, interleukin 27, interleukin 33, transforming growth factor beta 1, transforming growth factor beta 2, and interleukin 13, a nucleic acid molecule encoding such fusion protein, a vector comprising such nucleic acid molecule, and a host cell comprising such nucleic acid molecule or such vector. The invention further pertains to a method for producing such fusion protein. The fusion protein or a gene therapy vector encoding the fusion protein may be used in the prevention or treatment of a condition characterized by pathological pain, chronic pain, neuro-inflammation and/or or neurodegeneration.

The present invention provides methods for generating a mouse model that produces anti-polyethylene glycol (PEG) antibodies. Also provided are mice generated by said methods and methods of using these mice to screen PEG-containing products in vivo.

An object of the present invention is to provide a ventral hindgut organoid for producing a bladder organoid that comprises a layer structure of bladder epithelial cell types like the urinary bladder. An aspect of the present invention is to provide a method for producing a ventral hindgut organoid, comprising culturing a pluripotent stem cell with an inducer medium A containing activin A and GSK3β inhibitor to induce differentiation into definitive endoderm cells and culturing the definitive endoderm cells with an inducer medium B containing fibroblast growth factor, GSK3β inhibitor, and optionally further containing bone morphogenetic protein, and then culturing them in the presence of extracellular matrix with an inducer medium B containing fibroblast growth factor, GSK3β inhibitor, and optionally further containing bone morphogenetic protein to form a ventral hindgut organoid.

A nonhuman animal cancer model is described. The animal model includes an animal of the genus Peromyscus and xenograft cancer cells implanted in the animal. Methods for utilizing the animal model can include evaluation of growth and development of cancer cells, as well as evaluation of known and potential cancer treatment therapies. The animal model can be utilized to examine the efficacy of an anticancer therapy at the preclinical stage, can be utilized to screen potential cancer treatments in an individualized cancer treatment protocol, and can be utilized for identification of biomarkers associated with particular cancers and/or particular anticancer therapies, among other beneficial uses.

The present invention relates to a method of screening for a cancer therapeutic agent using Cyclin B1, Cyclin-dependent kinase 1 (CDK1), and retinoic acid receptor responder 1 (RARRES1), and a composition for diagnosing cancer or predicting a prognosis using the same. As a result of having conducted intensive studies to discover molecular mechanisms for diagnosing cancer and predicting a prognosis, the inventors of the present invention confirmed that in cancer-derived samples, according to the degree of mutual binding between RARRES1 and CDK1 or Cyclin B1, the mitosis of cancer cells was arrested, the formation of CDK1-Cyclin B1 complexes was suppressed, and the degradation of these proteins was promoted, and thus RARRES1 was a crucial factor in the diagnosis of cancer, prognosis prediction, and the treatment of cancer. In addition, through these findings, it is anticipated that RARRES1 may be widely used in screening for a cancer therapeutic agent exhibiting a decrease in the degree of binding between CDK1 and Cyclin B1, an increase in the degree of binding between the RARRES1 gene and CDK1 or Cyclin B1, and a decrease in an amount or activity of the CDK1 protein or the Cyclin B1 protein, and in the development of drugs. In addition, the present invention relates to a targeting vector including a portion of the Rarres1 gene and sequences used in producing a conditional knockout animal model, an animal cell for producing a tumorigenic animal model, which is produced using the targeting vector, a tumorigenic Rarres1.sup.−/− animal model produced using the animal cell, a method of producing the animal model, and a method of screening for a cancer therapeutic agent by using the method. Thus, as a result of having conducted intensive studies to discover molecular mechanisms for diagnosing cancer and predicting a prognosis, the inventors of the present invention confirmed that a Rarres1.sup.−/− animal model was prone to spontaneous tumors and exhibited increased phosphorylation of CDK1 and Cyclin B1 and a high activity of a CDK1-Cyclin B1 complex, and thus it was confirmed that the tumor cell cycle progression was unusually rapid due to a decrease in protein degradation ability. In particular, it was confirmed that stem cell proliferation was increased, and chromosomes were unstable upon induction of mitotic defects and mitosis, from which it was confirmed that RARRES1 is a crucial factor in diagnosing cancer, predicting a prognosis, and treating cancer. Moreover, it is anticipated that the Rarres1.sup.−/− animal model can be variously used for screening for a cancer therapeutic agent and developing a drug, through the relationship between RARRES1

Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Lymphocyte activation gene 3 (Lag3). The non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous Lag3 locus so that the non-human animals express a Lag3 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).

Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.