This mouse has been generated by targeted gene disruption. The mouse provides a model to investigate the function of the chemokine receptor CX3CR1, which is a proinflammatory receptor for the leukocyte chemoattractant CX3CL1 (aka fractalkine). As an example, the mouse is in use in the study of atherosclerosis. Further, the mouse may serve as a model study the role of the immune system during infection with pathogens as well as other immunologically mediated diseases and responses to tumors.

This invention discloses and covers polyphenolic compounds that will bind bacterial toxins, methods for the treatment of such infections, specifically Stx-1 toxins from STEC strains of E. coli.

Bacterial infections not only cause disease by their presence but also upon the release of toxins. The common enteric bacteria, E. coli O157:H7 releases such toxins (Stx-1) upon treatment with antibiotics. These toxins, when released into the lumen of the intestinal tract, will cause cellular damage thus increasing the severity of the infection.

Available for licensing are NIH patent pending contrast particles for use in MRI and flow cytometry to track cells migration in real time. Present cell-tracking studies rely on labeling cells with ultra-small dextran-coated iron particles that are endocytosed. The contrast agent of the present invention uses larger iron oxide particles, approximately 1 µm, situated in a tri-layer structure.

Gaucher disease, the most common lysosomal storage disease, is an inherited metabolic disorder in which harmful quantities of the lipid glucocerebroside accumulate in the spleen, liver, lungs, bone marrow and in rare cases in the brain, due to a deficiency of the enzyme glucocerebrosidase (Gba) that catalyses the first step in the biodegradation of glucocerebrosides. Type 1 Gaucher disease is the most common and is distinguished from the other forms of the disease, types 2 and 3, by the lack of neurologic involvement.

Diabetes affects over 120 million people worldwide (16 million in the US) and is a major health problem with associated health costs estimated at almost $100 billion dollars. Type 2 diabetes affects as many as 10% of the population of the Western World (with 15 million patients in the US alone) and arises from a heterogeneous etiology, with secondary effects from environmental influences. Risk factors for type 2 diabetes include obesity, high blood pressure, high triglycerides and age.

Cataract is the most common cause of blindness worldwide, with an estimated 25 million blind and 119 million visually impaired individuals worldwide. Over 20 million adults in the US alone are currently diagnosed with cataracts making this disease a major health concern. The incidence of cataract increases with age and a number of etiologic factors have been proposed in the pathogenesis of age-related cataract in humans including genetic factors, environmental factors and metabolic and biochemical changes in the crystalline lens.

Bitter taste has evolved in mammals as a central warning signal against ingestion of poisonous or toxic compounds. However, many beneficial compounds are also bitter and taste masking of bitter tasting pharmaceutical compounds is a billion dollar industry. The diversity of compounds that elicit bitter-taste sensations is vast and more than two dozen members of the TAS2R bitter taste receptor gene family have been identified.

This invention relates to the discovery that tristetraprolin (TTP) can promote the poly(A)RNase (PARN) mediated deadenylation of polyadenylated substrates containing AU-rich elements (AREs). As one aspect of the invention, the inventors have developed a cell free system that may be used for the purposes of assessing the effects of the various system components or their derivatives (i.e. AREs, PARN, or TTP) on the deadenylation process or the effects of various test agents on the deadenylation process.

The vanilloid receptor (VR) is a cation channel predominantly expressed on the peripheral processes and perikarya of nociceptive primary afferent neurons. Previous studies have shown that activation of the peripheral receptors by agonists such as capsaicin from hot peppers, or the much more potent resiniferatoxin, produces acute pain sensation which may be followed by desensitization. These inventors discovered that administration of VR agonists in the vicinity of neuronal cell bodies expressing the VR receptor can actually destroy those cells.

The invention includes a mouse in which the IL-21 receptor gene is disrupted by homologous recombination, the disruption being sufficient to prevent expression of the IL-21 receptor and thus to inhibit the action of IL-21. The invention also includes a mouse in which both the IL-21 receptor gene and the IL-4 gene are simultaneously disrupted in fashions being sufficient to inhibit the action of IL-21 and the production of IL-4. In a homozygous state, these mutations produce a mouse that has diminished B cell function.