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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.

The invention is a panel of five tests of patient sera for immune responses that may attack the brain and lead to the characteristic symptoms of pediatric acute neurologic syndrome (PANS). PANS is a condition defined by a sudden onset of obsessive-compulsive symptoms, eating restrictions, and other cognitive and/or behavioral symptoms. Currently, the diagnosis of PANS is made when other possible symptoms are ruled out, a diagnosis of exclusion.

The technology relates to the first radioligands that can be used to image and quantify the enzyme phosphodiesterase subtype D (PDE4D). The PDE4D proteins have a role in carrying out signal transduction pathways in several cell types and is thought to be the key target of various antidepressants. Current work with imaging the radioligands in monkey brains using positron emission tomography (PET) has been successful, and further work with humans is needed.

This technology relates to the generation and use of an antibody that recognizes the S1459 phosphorylated site of the GRIN2A gene, which encodes the GluN2A subunit of the NMDA receptor. This gene is widely accepted as an epilepsy-causative gene and has been implicated in autism spectrum disorder (ASD). The S1459 phosphorylation site was selected based on an identified mutation in an epilepsy patient. This antibody can be used to specifically visualize the localization of the phosphorylated version of the GRIN2A protein product in the brain.

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.

This technology relates to the therapeutic use of antibodies to decrease the potential neurodegenerative effect of the HERV-K retrovirus. Previous work has shown that patients with Amyotrophic Lateral Sclerosis (ALS) can have HERV-K activation. In animal models, activation of HERV-K can lead to neurodegenerative symptoms similar to those exhibited by ALS patients. This neurodegenerative effect is thought to be caused by the release of HERV-K envelope proteins into the extracellular space. Work with monoclonal antibodies in vitro has neutralized the toxicity of this protein.

This technology includes the creation and use of a mouse anti-Atlastin-1 monoclonal antibody (3194, IgG1). Mutations in Atlastin-1 are commonly found in hereditary spastic paraplegia, SPG3A. In addition, this protein is conserved in all eukaryotes, and it mediates fusion of endoplasmic reticulum tubules in cells, giving it its characteristic polygonal appearance. Thus, this protein is of interest to both those interested in disease pathogenesis and those studying basic cell biology.

This invention includes the generation and use of a polyclonal antibody for synapse-associated protein 102 (SAP102) and a polyclonal antibody that binds to mGluR7 when phosphorylated at Serine 862. Peptides of the sites were generated and injected into rabbits to create an immune response. Serum was collected from the rabbits that was then affinity purified. The specificity of the resulting polyclonal antibodies was then determined using biochemical techniques.

This invention includes human induced pluripotent stem cell (iPSC) lines that harbor a single copy dCas9-BFP-KRAB at the CLYBL safe harbor locus (mediating CRISPR inhibition of human gene expression) and/or a single copy of dox-inducible NGN2 at the AAVS1 locus (enabling the differentiation of the iPSCs into neurons). The CRISPR-mediated inhibition of human gene expression is maintained into the differentiated neurons, permitting functional studies of targeted genes in neurons.

This invention includes the generation and use of polyclonal antibodies that specifically recognize the glutamate receptor 1 protein that has been phosphorylated at Serine 567 (GluA1 pS567). Glutamate receptors are ligand-gated ion channels and are the predominant excitatory neurotransmitter receptor type in humans. A peptide sequence on the gene was selected surrounding the phosphorylation site. This peptide was then generated and injected into rabbits to create an immune response. Serum was then collected from the rabbit and the antibodies were affinity purified.