Mouse Models for the Study of Male Fertility

This technology includes two mouse models to be used in studying male sterility. One mouse is deficient in the full-length protein for STAMP/TtH5. The second is a conditional mutant STAMP mouse that can be used to produce tissues/organs that are deficient in full length STAMP. STAMP represents an intriguing new protein in the study of male fertility. More detailed future studies should identify the precise defect(s) leading to male sterility and may identify other behavioral and developmental consequences, such as a role in the immune system that is suggested by the microarray studies.

Treatment and Prevention of Neuropathic Pain with P2Y14 Antagonists

This technology includes the use of selective antagonist for the P2Y14 receptor for the treatment and prevention of neuropathic pain. Neuropathic pain conditions arising from injuries to the nervous system due to trauma, disease or neurotoxins are exceedingly difficult to treat. Clinicians and patients are often left to manage neuropathic pain with opioids, but these approaches are limited by the eventual loss in opioid efficacy with developing tolerance, the occurrence of severe adverse side effects and the strong potential for their abuse.

Mouse Model for the Study of Glycosphingolipid Storage Disorders

This technology includes a conventional knockout mice: beta- 1,4-N-acetylgalactosaminyl transferase 1 (GM2 Synthase) KO; B4galntltm1Rlp for the study of glycosphingolipid storage disorders. The glycosphingolipid (GSL) storage diseases are caused by genetic disruption in the lysosomal degradation pathway of GSLs, and include Tay-Sachs disease, Sandhoff's disease, Gaucher's disease, Fabry's disease, Krabbe's disease, and several others. In most of these diseases, GSLs accumulate to massive levels in cells, particularly in neurons, causing neurodegeneration and a shortened life span.

Truncated (N)-Methanocarba Nucleosides as Al Adenosine Receptor Agonists and Partial Agonists: Receptor Docking and Potent Anticonvulsant Activity for the Treatment of Various Conditions

This technology includes A1AR-selective agonists which are full or partial agonists of the A1AR and are being considered for treatment of various conditions: seizures, stroke, diabetes, pain, cardio-protection and arrhythmias. A1AR agonists are highly neuroprotective in ischemic and epileptic models. A1AR agonists are also being explored for antidepressant, antianxiety, and other neuropsychiatric effects, due to their presynaptic action to decrease the release of excitatory amino acids in the brain.

Sphingosine-1-phosphate 1 (S1P1) Receptor Signaling Mouse for Therapeutic Development

This technology includes a mouse model for studying SiP1 receptor signaling for development of therapeutics for a variety of conditions. The S1P1 receptor locus of the mouse has been modified by gene targeting to encode a fusion of the S1P1 receptor and the tetracycline-controlled activator protein (tTA) connected by a Tobacco Etch Virus (TEV) cleavage sequence, internal ribosome initiation sequence (IRES), followed by a beta-arrestin-Tobacco Etch Virus (TEV) protease fusion protein. When activated, the modified S1P1 receptor binds the beta-arrestin-TEV protease fusion, which cleaves the tTA.

Eukaryotic Transposase Mutants and Transposon End Compositions for Modifying Nucleic Acids and Methods for Production and Use in the Generation of Sequencing Libraries

This technology includes novel hyperactive Hermes Transposase mutants and their encoding genes. These transposases are easily purified in large quantity after expression in bacteria. The modified Hermes Transposases are soluble and stable and exist as smaller active complexes compared to the native enzyme. The consensus target DNA recognition sequence is the same as the native enzyme and shows minimal insertional sequence bias.

Phenotypic Screening for Treating Chronic Neuropathic Pain: Focus on 2-Arylethynyl Substitution of A3 Adenosine Agonists

This technology includes (N)-methanocarba derivatives that are selective agonists of the A3 receptor to be used for the treatment of chronic neuropathic pain. This class of compounds produced full agonists of the human A3AR of nanomolar affinity that were consistently highly selective (>1000-fold vs. A1AR and A2AAR). The selectivity at mouse A3 receptors is smaller, but the compounds are still effective in vivo in reducing or preventing development of neuropathic pain.

Figla-Cre Transgenic Mice Expressing Myristoylated EGFP in Germ Cells as a Model for Investigating Perinatal Oocyte Dynamics

This technology includes a transgenic mouse model which can be used to study perinatal oocyte dynamics. In the first two days after birth, the number of primordial ovarian follicles and their germ cells undergo a major decrease. The mechanism for this decrease was studied. Ablation of FIGLA (Factor in the germline, alpha), a basic helix-loop-transcription factor, results in massive perinatal oocyte loss. A transgenic mouse line was established, Figla-EGFP /Cre, in which EGFP and Cre recombinase are expressed just before birth in germ cells.

Methanocarba-7-Deazaadenosine Analogues as Inhibitors of Adenosine Kinase for the Prevention of Seizures

This technology includes new nucleoside inhibitors containing rigid rings that provide high potency for use as antiepileptic drugs. Adenosine kinase (AdK) inhibitors raise the level of endogenous adenosine, particularly in disease states, and are of interest for the potential treatment of seizures and neurodegenerative and inflammatory conditions.

Adenosine Receptor Binding Compounds with Subtype and Functional Selectivity for Therapeutic Development

This technology includes adenosine receptor binding compounds which could potentially be used for development of more selective and safe treatment of cardiovascular, psychiatric and neurodegenerative disorders. Though adenosine has been extensively studied as a primary chemical scaffold for adenosine receptor agonists, very little structure activity data exist for C5' substitution. This technology presents novel rationally designed small molecule compounds capable of selective binding to adenosine receptor (subtypes A2a, A1, A2b and A3) and inducing effector-biased downstream signaling.