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This technology includes PPTN which can be used to study treatments of inflammatory diseases. PPTN is currently a useful pharmacological probe that many labs in the field of purinergic signaling are interested in obtaining. The availability of PPTN as a research tool will stimulate basic advances in the field and possibly eventually lead to new treatments. However, PPTN itself is unsuitable for therapeutic applications. Separately, we are working on new and improved antagonists of the P2Y14 receptor.

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.

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.

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.

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.

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.

This technology includes lentivirus vectors to be used to treat sickle cell disease and beta thalassemia. (i) Lin28A or Lin28B vectors designed for erythroid-specific expression using EKLF1, SPTA1, or similar erythroid-specific regulatory elements will be used to transduce hematopoietic stem cells isolated from humans with sickle cell disease or beta-thalassemia syndromes.

This technology includes transgenic mice in which designer rat M3 muscarinic receptor mutants were expressed only in islet 13-cells (directed by rat insulin promoter II), were unable to bind acetylcholine (the endogenous ligand) but could be selectively activated by an otherwise pharmacologically inert compound (clozapine-N-oxide (CNO)). The R-q receptor contained a Y148C point mutation, which enabled CNO to selectively activate G proteins of the Gq/11 family. The R-5 receptor contained an A238G mutation, which enabled CNO to selectively activate G proteins of the G5 family.

This technology includes identification of the wild mouse microbiome as a method to increase resistance to lethal viral infection. We establish that the gut microbiome of barrier-raised C57BL/6 mice is dysbiotic compared to that of their outbred, wild-living progenitors, Mus musculus domesticus. We find that the multigenerational offspring of pregnant germfree C57BL/6 mice reconstituted with the gut microbiome of wild mice exhibit a less inflammatory response and increased survival following influenza A virus infection.

Feedback vasodilation by endothelium-derived nitric oxide (NO) is under the regulation of globins. NIH Researchers discovered that not only the alpha globin but also the beta globin subunits of hemoglobin are expressed in the human artery wall, with beta globin interacting directly with endothelial nitric oxide synthase (eNOS).