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This invention concerns "knockout" animals, including mice, which have a deficit of functional steroid hormone receptors, DNA constructs containing the mutations, and methods for producing the animals. The mutation is introduced into the animal or its ancestors at an embryonic stage. These knockout animals provide a model system for studying the biological role of hormones, including steroid hormones and sex steroids, in growth, development, morphological differentiation, and sexual and reproductive behavior and cycles, etc.

Biological radicals resulted from oxidative stress has been implicated in human diseases, such as cancer and aging. There is, however, a paucity of reliable methods for in vivo or ex vivo detection of either radical formation, the end-products of radical formation or susceptibility for radical formation. The chicken polyclonal anti-DMPO can be used to detect the stable nitrone end-product of protein and DNA radicals in ELISA assays, blot analyses and confocal microscopy.

Biological radicals resulted from oxidative stress has been implicated in human diseases, such as cancer and aging. There is, however, a paucity of reliable methods for in vivo or ex vivo detection of either radical formation, the end-products of radical formation or susceptibility for radical formation. The Rabbit polyclonal anti-DMPO can be used to detect the stable nitrone end-product of protein and DNA radicals in ELISA assays, blot analyses and confocal microscopy.

The estrogen-related receptor alpha (ERRalpha) and proliferator-activated-receptor-gamma coactivator-1alpha (PGC-1alpha) play major roles in transcriptional control of cellular energy metabolism. In particular ERRs are required for the response to various environmental challenges that require high energy levels by the organism. As central regulators of energy homeostasis, ERRs may also implicate in the etiology of metabolic disorders, such as type 2 diabetes and metabolic syndrome.

Leucine rich repeats and calponin homology containing protein 4 (Lrch4) is a gene that encodes a protein predicted to have a C-terminal transmembrane domain, a calponin homology domain, and 5-8 leucine rich repeats (LRRs). We silenced Lrch4 in RAW 264.7 macrophages as well as CD14-MD2-TLR4-HEK293 cells and found that Lrch4 knockdown attenuates responsiveness of cells to LPS and other pathogen-associated molecules. These findings suggest that Lrch4 is a regulator of the innate immune response.

CAR (nuclear constitutive active receptor) is a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. It is primarily responsible for sensing foreign toxic substances and in response up regulating the expression of proteins involved in the detoxification and clearance of these substances from the body. CAR is constitutively active in the absence of a ligand but is regulated by both agonists and inverse agonists.

Tristetraprolin (TTP) is the prototype member of a small family of RNA binding proteins that bind to specific types of AU-rich elements in the 3'UTRs of target mRNAs and promote their rapid turnover. One of the targets destabilized by TTP is Tumor necrosis factor alpha (TNF). TNF has long been a target of anti-inflammatory drug development, in which recombinant protein molecules based on TNF antibodies or TNF receptors have been used to bind directly to TNF and inactivate it.

Electron Spin Resonance (ESR) is an universal, specific tool for the detection of free radicals in biological systems. Its application to the investigation of free radicals from whole animals, organs, and cells has been made possible by the spin-trapping technique. In a Spin-trapping experiment, a spin trap such as DMPO (5,5-dimetryl-1-pyrroline N-oxide) reacts specifically with one or more types of free radical to form radical-derived nitrone adducts that are much more stable than the original free radicals.

Mutations in the p53 gene are associated with 50% of all cancers and nearly 80% of the p53 mutations are missense changes. We have developed genetic assays based in yeast that can functionally categorize expressed p53 mutant proteins. The combined assays are referred to as the FIP53 system. Because human p53 cDNA can be conveniently cloned in yeast, the FIP53 system provides a rapid and sophisticated system for the functional analysis of p53 mutants. Four categories of mutations have already been identified.

Tristetraprolin (TTP) is involved in the physiological regulation of the secretion of at least two important cytokines, tumor necrosis factor alpha (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). TTP exerts its effects by directly binding to the mRNAs encoding these proteins and destabilizing them, resulting in less secretion. Conversely, TTP deficiency results in an excess of both cytokines, leading to a systemic inflammatory syndrome.