Methods treating an aberrant activation of v3 integrin are provided. The methods include administering a therapeutically effective amount of inducible co-stimulator ligand (ICOSL) polypeptide to a subject in need thereof. Methods of identifying subjects having a kidney injury are also provided.

The present invention has found that chimeric animals suffer from noticeable inflammation after birth, though neither immune response nor inflammation in the fetal period of these animals has been reported hitherto. This is an unexpected finding since chimeric animals in the fetal period were exclusively analyzed in prior studies and thus it is deemed that immunotolerance has been theoretically established therein. The present invention provides a composition for suppressing immune response or inflammation in the fetal period of a born chimeric animal.

In some aspects, the disclosure relates to compositions and methods for modulating (e.g., increasing and/or decreasing) bone mass in a subject. In some aspects, the disclosure provides isolated nucleic acids, and vectors such as rAAV vectors, configured to express transgenes that promote (e.g., increase) or inhibit (e.g., decrease) activity, differentiation, or function of certain types of bone cells, for example osteoblasts, osteoclasts, osteocytes, etc. In some embodiments, the isolated nucleic acids and vectors described by the disclosure are useful for treating disorders and conditions associated with increased bone mass (e.g., osteopetrosis) or decreased bone mass (e.g., osteoporosis).

In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for reducing addiction to alcohol, and for ameliorating, reversing, treating or preventing Alcoholic Liver Disease (ALD), or alcohol-induced brain injury, wherein optionally the alcohol-induced brain injury comprises neuronal death and astrogliosis (reducing alcohol-induced neuronal death and astrogliosis). In alternative embodiments, provided methods for administering to the individual in need thereof a compound or composition capable of inhibiting or decreasing the expression or activity of an IL-17 or IL-17 receptor (IL-17R) or RORt protein, transcript and/or gene to treat or for use in: reducing addiction to alcohol; or ameliorating, reversing, treating or preventing Alcoholic Liver Disease (ALD) or alcohol-induced brain injury; or, inhibiting ROR t to effectively block production of IL-17 cytokines and attenuate development of alcohol-induced liver fibrosis and brain damage.

A method for changing a condition of an eyelid of a hairless animal, a model animal for evaluating a therapeutic or prophylactic effect against an eyelid disease obtained by the method, a method for producing the model animal, a method of screening using the model animal and a substance having a therapeutic or prophylactic effect against an eyelid disease selected by the method of screening, and a therapeutic or prophylactic agent against an eyelid disease containing the substance as an active ingredient.

Methods and compositions for introducing genetic mutations into non-human animal cells are provided. These cells can be used to produce animal models of human disease. In some embodiments, the genetic mutations are flanked by DNA sequences that are humanized to match homologous DNA sequences. In some embodiments, the animal model is a large mammalian model for an inherited metabolic disorder. In some embodiments, the animal model is a pig model for phenylketonuria (PKU) created by introducing a missense mutation into exon 8 of the Pah gene.

Methods and compositions are described herein that promote bone formation. Such methods and compositions include SLIT3 or SLIT2 agents that can be administered to a subject (e.g., one in need thereof). Methods are also described herein that reduce or prevent unwanted bone formation. Such methods can involve administering an inhibitor of SLIT3 or SLIT2 to a subject.

Provided are a non-human model animal of a retinal vascular disease that can favorably show symptoms similar to those of human retinal vascular diseases such as human diabetic retinopathy, and a method for producing the non-human model animal. In particular, provided are a non-human model animal that is suitable for establishing a method for treating, preventing, or diagnosing retinal edema, which causes highly impaired vision, and a method for producing the non-human model animal. A method for screening a drug for treating and preventing a retinal vascular disease, the method using a non-human model animal, is provided. Provided are a non-human model animal of a retinal vascular disease in which constitutively active Akt is expressed, a method for producing a non-human model animal of a retinal vascular disease in which constitutively active Akt is expressed, and a method for screening a drug for treating or preventing a retinal vascular disease.

A lentiviral vector system for expressing a lentiviral particle is disclosed. The lentiviral vector system includes a therapeutic vector. The lentiviral vector system produces a lentiviral particle for upregulating PAH expression in the cells of a subject afflicted with phenylketonuria (PKU).

The invention relates to methods of treating a subject having a muscle disorder by identifying a subject having a muscle disorder in need of treatment; injecting human myogenic precursor cells in an amount capable of forming mature muscle tissue into a portion of a limb of the subject; subjecting a nerve of the limb to therapeutic stimulation configured to enhance engraftment of the human myogenic precursor cells; and creating a graft of the human myogenic precursor cells to promote generation of mature muscle tissue, wherein the generation of mature muscle tissue improves muscle function. Preferably, the subject is a mammal, such as a human or a non-human mammal. In some embodiments, the non-human mammal is immunocompromised and the limb is irradiated. The engraftment can be promoted by a means other than therapeutic electrical stimulation (preferably intermittent neuromuscular electrical stimulation), for example by exercise.