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Recent studies have identified the G-protein-coupled receptor (GPCR) for insulin-like 3 peptide (INSL3), relaxin family peptide receptor 2 (RXFP2), as an attractive target for the treatment of bone diseases such as osteoporosis and rare bone diseases such as osteogenesis imperfecta. Currently, the most effective available treatment for osteoporosis is an expensive hormone therapy that requires daily injections. A stable, orally deliverable drug is a much more desirable alternative. Our RXFP2 agonists perform as well as the natural ligand INSL3 in cellular assays.

Congenital disorders of glycosylation (CDGs) are inherited disorders of abnormal protein glycosylation that affect multiple organ systems. More than 100 different CDGs have been described, affecting protein and lipid glycosylation. NHGRI investigators have been able to isolate fibroblasts from patients with PMM2 (phosphomannomutase)-CDG, also known at CDG type Ia, which is an inherited, broad-spectrum disorder with developmental and neurological abnormalities.

This technology includes a transgenic mouse model of Niemann-Pick Disease Type C (NPC), which is a rare neurodegenerative disorder, characterized by intracellular accumulation of cholesterol and gangliosides. The mouse strain, Tg(Npcl), expresses wild-type NPC1 gene under the control of the prion promoter. When combined with the NPC deficient mouse model, BALB/c npcnih/nih, also known as Npcl-/-, the transgene insertion allele rescues life expectancy of Npc1-/- mice. Npc1-/- mouse have reduced life expectancy and die around 8 weeks, making it a difficult model to be utilized.

These patent applications describe the cloning and characterization of the full-length genome of adeno-associated virus type 4 (AAV4). AAV4, like other members of the AAV family, may be useful as a vector for gene therapy.

This technology includes transgenic mice to be used in the study of melanocyte stem cells (MSCs) for utilization in regenerative medicine. Using the melanocyte system as a model, we investigated establishment of MSCs in the hair bulge - the stem cell compartment of the hair. During embryogenesis, all melanoblasts express SOX10, but this expression is downregulated during hair follicle morphogenesis and MSC differentiation. To further study the role of SOX10, we generated transgenic mice overexpressing SOX10 in melanoblasts.

This invention relates to a novel gammaretroviral vector packaging cell line and a method of producing gammaretroviral vectors suitable for gene therapy. The described vectors may contain the gibbon ape leukemia virus (GALV) envelope with a CD11D8 epitope tag enabling their purification on a monoclonal antibody conjugated column. These vectors have several advantages over existing systems, including a broader host range, higher infectivity, and lower potential for replication.

This technology relates to a mouse model that improves an existing method of disrupting the production of the BDNF protein in specific parts of the brain. A current avenue of research seeks to examine how gene expression may effect long-lasting changes in the nervous system. Previous work has resulted in a mouse line in which the production of BDNF was disrupted. However, these mice had an inadvertent genetic component left in: a neomycin cassette. This unintentional addition led to significant deleterious effects.

This invention relates to novel mouse and rat models that permit the temporal death of neuronal precursor cells at any time point. Other existing methods of decreasing neurogenesis are relatively non-specific (e.g., injecting glucocorticoids) or require expensive equipment (e.g., focal x-irradiation)
These mice and rats are being used to inhibit adult neurogenesis in order to study the normal function of adult neurogenesis and to model disease states thought to feature decreased neurogenesis, such as chronic stress, anxiety, and depression.

This invention relates to the stable and high-yield production of a high-potency toxin protein called DT390-EGF. This toxin was developed for the treatment of EGF-receptor-positive cancers, including bladder cancer. Initial methods for synthesizing DT390-EGF relied on the use of E. coli. However, the production in E. coli was difficult to prepare and had limited stability. Repeated efforts to standardize the process in E. coli gave poor yields, purity, and high variation.

This technology includes the generation and use of an antibody that can detect endogenous Neuroligin 4Y, NLGN4Y, a cell adhesion molecule on the X-chromosome. NLGN4Y is part of an X-Y pair with NLGN4X, which has been implicated with autism spectrum disorder (ASD) and intellectual disability. ASD has a sex bias etiology that is not well understood, affecting four times as many males as females. Previous work has revealed a potential pathogenic mechanism for male-bias based on mutations in NLGN4X and NLGN4Y. The use of the NLGN4Y antibody could be used to study potential mechanisms.