Provided are a transgenic animal model, a method for constructing same, and use thereof. An Axin1flox/flox transgenic mouse is used to mate with an Agc1-CreER transgenic mouse to produce an Axin1+Agc1ER condition knockout mouse. Then by means of tamoxifen induction, the Axin1 expression in the Axin1+Agc1ER condition knockout mouse is down-regulated, and a disease combined model with the pathological characteristics of growth plate chondrocyte hypertrophy, heterotopic ossification and articular cartilage degeneration of knee joints is successfully established. The model is similar to clinically related pathological features, and can be used for systematically studying the pathogenesis of growth plate chondrocyte hypertrophy, heterotopic ossification and osteoarthritis and further screening for drugs for treating related diseases.

Provided are a posttraumatic stress disorder (PTSD) animal model in which dopamine receptor subtype 4 (D4R) is damaged or deficient, a method for preparing the same, a method for screening a drug for treating PTSD using the same, and a pharmaceutical composition for treating PTSD comprising a drug detected by the screening method. As it is identified that a specific type of dopamine receptor is associated with a mechanism for fear memory expression induced by long-term depression (LTD), the understanding of pathogenesis of PTSD may be heightened, the animal model exhibiting similar clinical conditions of PTSD and the method for preparing the same may be applied in analyses for stability and effectiveness of a therapeutic agent for PTSD and screening of a therapeutic drug. Further, an agonist of D4R contained in the composition has been approved by the US FDA and clinically used for psychiatric diseases such as schizophrenia, and thus may be immediately used for clinical applications for PTSD symptoms.

A transgenic non-human mammal has a genome that includes an early-immediate enhancer of human cytomegalovirus (CMV enhancer), a -actin promoter and the entire gene region of human matrix metalloproteinase 2 (hMMP2) disposed downstream of the promoter. The hMMP2 is systemically expressed in the transgenic non-human mammal, which thus provides a suitable animal model for studying chronic obstructive pulmonary disease and related diseases and conditions.

Disclosed herein are novel compositions and methods for the treatment of age-related diseases, mitochondrial diseases, the improvement of stress resistance, the improvement of resistance to hypoxia and the extension of life span. Also described herein are methods for the identification of agents useful in the foregoing methods. Methods and compositions are provided for the treatment of diseases or disorders associated with mitochondrial dysfunction. The invention relates to methods for treatment and prevention of cancer by administering agents that increase levels of NAD+, such as NAD+ precursors or agents involved in NAD+ biosynthesis.

This invention provides compositions of active highly phosphorylated lysosomal sulfatase enzymes, their pharmaceutical compositions, methods of producing and purifying such lysosomal sulfatase enzymes and compositions and their use in the diagnosis, prophylaxis, or treatment of diseases and conditions, including particularly lysosomal storage diseases that are caused by, or associated with, a deficiency in the lysosomal sulfatase enzyme.

This invention provides compositions of active highly phosphorylated lysosomal sulfatase enzymes, their pharmaceutical compositions, methods of producing and purifying such lysosomal sulfatase enzymes and compositions and their use in the diagnosis, prophylaxis, or treatment of diseases and conditions, including particularly lysosomal storage diseases that are caused by, or associated with, a deficiency in the lysosomal sulfatase enzyme.

Provided are long-acting nerve growth factor (NGF) polypeptides comprising from N-terminus to C-terminus an NGF moiety and an Fe moiety, methods of making, and uses thereof.

This invention relates to a pharmaceutical composition for treatment of a bone disease comprising, as an active ingredient, a protein comprising an extracellular cysteine-rich domain, which is from the Frizzled receptor selected from the group consisting of mammalian animal-derived Frizzled 1, Frizzled 2, and Frizzled 7 and has activity of increasing bone mass, bone density, and/or bone strength, or a mutant of such domain having sequence identity of 85% or higher to the amino acid sequence of the domain and having activity of increasing bone mass, bone density, and/or bone strength, or a vector comprising a nucleic acid encoding the protein.

The present invention provides non-human animal models of neuronal injury and/or cognitive dysfunction and methods of making and using such animal models. The animal models of the invention are particularly suited to assessing neurodegeneration in selected regions of interest in the CNS, and thus especially useful for testing the therapeutic efficacy of agents targeting neurodegeneration associated with aging, neurodegenerative diseases, autoimmunity and trauma (e.g., ischemia).

Methods of producing non-human animal models of corneal angiogenesis and corneal ectatic diseases, such as corneal keratoconus, by applying an aromatic compound to the eye of a non-human animal are described. Also described are non-human animal models of corneal angiogenesis and corneal ectatic diseases, and methods of using the non-human animal models to screen compounds that modulate corneal angiogenesis and corneal ectatic diseases.