Abstract: The present invention provides GPCR polypeptides and polynucleotides, recombinant materials, and transgenic mice, as well as methods for their production. The polypeptides and polynucleotides are useful, for example, in methods of diagnosis and treatment of diseases and disorders. The invention also provides methods for identifying compounds (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for treating conditions associated with GPCR dysfunction with the GPCR polypeptides, polynucleotides, or identified compounds. The invention also provides diagnostic assays for detecting diseases or disorders associated with inappropriate GPCR activity or levels.

Abstract: The invention relates to a transgenic mouse model with deficient respiratory chain function in dopamine (DA) neurons. By suppressing or deleting the mitochondrial transcription factor A (Tfam) in DA neurons, a mouse model is obtained, which reproduces key pathophysiological features of Parkinson's disease (PD), i.e., slow progressive loss of DA terminals in striatum and loss of DA neurons in substantia nigra pars compacta; alpha-synuclein immunoreactivity including intracellular inclusions similar to Lewy bodies in affected areas prior to and during cell loss; progressive movement disorder associated with abnormal gait, tremor and rigid limbs. The mouse model can be used to develop pharmacological, gene therapy or cell therapy treatments for PD.

Abstract: The present invention relates to a novel animal model for neurological degenerative diseases, especially autism, relating to overexpression of human secreted APP-alpha. This novel animal model exhibits several aspects of amyloidopathy. The present invention also relates to a method for producing the double transgenic animals, to cells and cell lines derived from these animals. Moreover, a method for the evaluation of the in vivo effects of a test compound on secreted APP-alpha expression and autism pathology in these animals is provided.

Abstract: This invention pertains to chemometric methods for the analysis of chemical, biochemical, and biological data, for example, spectral data, for example, nuclear magnetic resonance (NMR) spectra, and their applications, including, e.g., classification, diagnosis, prognosis, etc., especially in the context of bone disorders, e.g., conditions associated with low bone mineral density, e.g., osteoporosis.

Abstract: The genome of the non-human mutant mammal, deficient in an endogenous Sigma receptor, contains a mutation that comprises a disruption in an endogenous Sigma receptor gene, wherein said gene disruption gives rise to a mutant lacking detectable levels of endogenous Sigma receptor. The mutant may be used as a control animal for in vivo tests, as well as a source of cells that can be used in in vitro tests. Mutants deficient in the Sigma-1 receptor can be used as models for in vivo study of disorders of the central nervous system, memory alterations, stress conditions and drug addictions, analgesia processes and neuroprotection. Mutants deficient in the Sigma-2 receptor can be used to study diagnostic or therapeutic tools to fight cancer and/or degenerative processes and/or to design compounds capable of preventing, reducing or alleviating the secondary pathology associated with administration of neuroleptic agents.

Abstract: The object of the invention is a method for the production of a non-human transgenic mammal by means of which it is possible to monitor in vivo and in all the tissues the state of activation of any intracellular receptor, utilising a reporter gene inducible by natural or synthetic molecules which modulate the activity of such receptor. The mammal is question is preferably a mouse.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO57290 genes. Such in vivo studies and characterizations may provide valuable identification and discovery of therapeutics and/or treatments useful in the prevention, amelioration or correction of diseases or dysfunctions associated with gene disruptions such as cardiovascular, endothelial or angiogenic disorders; immunological disorders; oncological disorders; bone metabolic abnormalities or disorders; or developmental abnormalities.

Abstract: The invention relates to novel assays for the in vivo analysis of neurodegenerative diseases and the use of such assays to discover therapies capable of modulating such diseases.

Abstract: Arterial and venous endothelial cells are molecularly distinct from the earliest stages of angiogenesis. This distinction is revealed by expression on arterial cells of a transmembrane ligand, called EphrinB2 whose receptor EphB4 is expressed on venous cells. Targeted disruption of the EphrinB2 gene prevents the remodeling of veins from a capillary plexus into properly branched structures. Moreover, it also disrupts the remodeling of arteries, suggesting that reciprocal interactions between pre-specified arterial and venous endothelial cells are necessary for angiogenesis. This distinction can be used to advantage in methods to alter angiogenesis, methods to assess the effect of drugs on artery cells and vein cells, and methods to identify and isolate artery cells and vein cells, for example.

Abstract: The present invention relates to a transgenic non-human mammalian animal whose genome incorporates a biosensor of the activity of modulators of cell proliferation consisting of a DNA sequence that comprises the luciferase reporter transgene ligated downstream of a promoter sequence of the CYCB2 gene, this sequence promoter/reporter being flanked by HS4 insulator sequences at each of its 3? and 5? sides. The transgenic animal is proposed for the screening of compounds with pharmacologically relevant activities. The invention provides for a further use of the animal line for the study and toxicological evaluation of compounds with tumorigenic activity, and also for the study and evaluation of compounds with chemopreventive anti-cancer activity.

Abstract: This invention provides methods of screening compounds for their ability to alter the production of A?(x?41) alone or in combination with A?(x?40). The methods involve administering compounds to cells, specifically measuring the amounts of A?(x?40) and A?(x?41) produced by the cells, and comparing these amounts to that produced by the cells without administration of the compounds.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO227, PRO233, PRO238, PRO1328, PRO4342, PRO7423, PRO10096, PRO21384, PRO353 or PRO1885 genes. Such in vivo studies and characterizations may provide valuable identification and discovery of therapeutics and/or treatments useful in the prevention, amelioration or correction of diseases or dysfunctions associated with gene disruptions such as neurological disorders; cardiovascular, endothelial or angiogenic disorders; eye abnormalities; immunological disorders; oncological disorders; bone metabolic abnormalities or disorders; lipid metabolic disorders; or developmental abnormalities.

Abstract: The present invention provides transgenic, large non-human animal models of diseases and conditions, as well as methods of using such animal models in the identification and characterization of therapies for the diseases and conditions.

Abstract: The present invention provides GPCR polypeptides and polynucleotides, recombinant materials, and transgenic mice, as well as methods for their production. The polypeptides and polynucleotides are useful, for example, in methods of diagnosis and treatment of diseases and disorders. The invention also provides methods for identifying compounds (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for treating conditions associated with GPCR dysfunction with the GPCR polypeptides, polynucleotides, or identified compounds. The invention also provides diagnostic assays for detecting diseases or disorders associated with inappropriate GPCR activity or levels.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO218, PRO228, PRO271, PRO273, PRO295, PRO302, PRO305, PRO326, PRO386, PRO655, PRO162, PRO788, PRO792, PRO940, PRO941, PRO1004, PRO1012, PRO1016, PRO474, PRO5238, PRO1069, PRO1111, PRO1113, PRO1130, PRO1195, PRO1271, PRO1865, PRO1879, PRO3446, PRO3543, PRO4329, PRO4352, PRO5733, PRO9859, PRO9864, PRO9904, PRO9907, PRO10013, PRO90948, PRO28694, PRO16089, PRO19563, PRO19675, PRO20084, PRO21434, PRO50332, PRO38465 or PRO346 genes.

Abstract: The present invention provides compositions and methods for regulating remyelination and promoting oligodendrocyte differentiation by modulating GM98 (also known as MRF) expression and activity. Compositions and methods for treating neuropathies and screening for bioactive agents are also provided herein.

Abstract: Methods for restoring a desired pattern of DNA methylation, inducing re-expression of methylation-silenced tumor suppressor genes (TSGs), and/or inhibiting tumorigenicity both in vitro and in vivo in a subject in need thereof by administering an effective amount of one or more miR-29s sufficient to target one or more of DNMT3A and DNMT3B are disclosed.

Abstract: The invention provides methods of determining in situ the EMT status of the cells of a tumor in a patient in vivo, including: (a) providing an EMT-status-detecting conjugate containing an antibody that binds to an EMT-status biomarker, and a reporter molecule; (b) introducing the conjugate into a patient with a tumor, such that the conjugate contacts the EMT-status biomarker of the cells of the tumor; (c) employing a means for detection of the signal from the conjugate at the tumor site; and (d) using a means for image analysis to localize and quantify the signal from the conjugate at the tumor site, a positive signal indicating the presence of epithelial tumor cells if the EMT-status biomarker is an epithelial biomarker, and mesenchymal tumor cells if the EMT-status biomarker is a mesenchymal biomarker.

Abstract: The invention provides transgenic animals comprising a disruption in the endogenous GPR101 gene and methods of producing such transgenic animals. The invention further provides methods of identifying compounds that modulate GPR101 receptor proteins.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO226, PRO257, PRO268, PRO290, PRO36006, PRO363, PRO365, PRO382, PRO444, PRO705, PRO1071, PRO1125, PRO1134, PRO1155, PRO1281, PRO1343, PRO1379, PRO1380, PRO1387, PRO1419, PRO1433, PRO1474, PRO1550, PRO1571, PRO1572, PRO1759, PRO1904, PRO35193, PRO4341, PRO4348, PRO4369, PRO4381, PRO4407, PRO4425, PRO4985, PRO4989, PRO5737, PRO5800, PRO5993, PRO6017, PRO7174, PRO9744, PRO9821, PRO9852, PRO9873, PRO10196, PRO34778, PRO20233, PRO21956, PRO57290, PRO38465, PRO38683 or PRO85161 genes.

Abstract: In a first aspect, cyclic peptides are provided identified as molecules altering the interferon activity, namely, inhibiting interferon response. Moreover, the present invention relates to a transgenic animal or parts thereof and a method for the determination of molecules and compounds altering the function of interferons, in particular, type I and type II interferon. In particular, said transgenic animal or parts thereof contain large parts of exogenous chromosomal DNA, namely interferon responsive DNA promoter elements operably linked with a nucleic acid sequence encoding a reporter or marker molecule. These a transgenic animal or parts thereof are useful in the methods according to the present invention.

Abstract: Provided are methods of treating rheumatoid arthritis by inhibiting Neuromedin U signalling.

Abstract: Human GFAT genes are identified as modulators of the Axin pathway, and thus are therapeutic targets for disorders associated with defective Axin function. Methods for identifying modulators of Axin, comprising screening for agents that modulate the activity of GFAT are provided.

Abstract: The present invention provides a method for assessing embryotoxicity of a chemical comprising: (1) a first step of measuring the expression level of one or more genes selected from among genes each comprising any of the nucleotide sequences of SEQ ID NOs: 1 to 78 and 101 to 230 and orthologous genes thereof in a sample from a non-human mammal or mammalian cell which has come into contact with a test chemical; and (2) a second step of comparing the measured value of the expression level of the gene in the sample obtained in the first step with a control value of the expression level of the gene and based on the difference assessing the level of the embryotoxicity of the test chemical in the sample; and so on.

Abstract: The present invention relates to a composition comprised of AKAP12 (A-Kinase anchoring protein 12) and to uses of AKAP12 mutant zebrafish as an animal model. More particularly, the following characteristics are noted in the present AKAP12 mRNA knockdown zebrafish: crooked or shortened tail, inability to move normally, non-uniform micro-vasculature in the brain, and change in heart shape with non-uniform and weak heartbeats. It also has various circulatory and genetic defects, such as hemorrhage from the ventricles of the heart, brain, and retina. All of these defects can be cured with AKAP12 injection. Therefore, AKAP12 can be used as an active component for a composition to prevent and heal circulatory and genetic defects that are caused by AKAP12 deficiency, and as a hemorrhage inhibitor. Further, the AKAP12 deficient mutant zebrafish can be useful as an animal model for verification of effectiveness of treatment for genetic defects in the circulatory system.

Abstract: A transgenic animal model for evaluating growth, survival and/or metastasis of xenotransplanted normal or tumor cells or tissue is disclosed, in which a human growth factor, hHGF stimulates growth in vivo of human cells or tissue. A strain of Tg mice on the C3H background that is immunocompromised as a result of a homozygous scid gene has been bred which express a nucleic acid encoding hHGF/SE The ectopically expressed hHGF/SF ligand significantly enhances growth of human tumor cell lines and explanted tumor cells or tissue that express the Met receptor for hHGF. Such animals also have an enlarged normal livers and greater than normal liver regenerative capacity. Any Met-expressing hHGF-dependent human cells, including hepatocytes and various stem cells can survive and grow in such animals.

Abstract: An object of the present invention is to develop a probe for measuring in real time the kinetics of CREB or actin closely related to brain functions such as memory formation in live animals.

Abstract: The invention relates to cells and transgenic non-human mammals having at least one disrupted heparanase allele. The invention further relates to methods of screening therapeutic drug candidates utilizing the heparanase deficient non-human mammals and cells.

Abstract: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity Fc?R locus, and wherein the mouse is capable of expressing a functional FcR?-chain. Genetically modified mice are described, including mice that express low affinity human Fc?R genes from the endogenous Fc?R locus, and wherein the mice comprise a functional FcR?-chain. Genetically modified mice that express up to five low affinity human Fc?R genes on accessory cells of the host immune system are provided.

Abstract: The present invention relates to methods and compositions for high content drug screening in C. elegans which may be used to identify compounds that treat disorders associated with protein aggregation.

Abstract: The present invention provides a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to drug transport sensitivity or resistance drug transport resistance or sensitivity. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a drug transporter gene such as the Slc7a11 (NC_005101.2) gene, the Abcb1 (NC_005103.2) gene, etc. The present invention also provides a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to drug transport sensitivity or resistance drug transport resistance or sensitivity. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a drug transporter gene.

Abstract: An animal model has been developed where the animals can survive myocardial infarctions caused by diet-induced coronary atherosclerosis, and live with chronic heart failure. This animal model is a result of reduced activity of scavenger receptor class BI (SR-BI) and ApoE and the inducible activity of the Mx1-Cre gene. In a preferred embodiment, the model is a result of crossbreeding two transgenic mouse lines: a knockout of SR-BI (SRBI?/?) and an impaired ApoE expressor (Apoeh/h) to generate a strain referred to as Apoeh/hSRB1?/? mice, which is then crossbred to mice that carry the inducible Mx1-Cre transgene. The Apoeh/hSRB1?/? mouse model is genetically modified, enabling the offspring to rapidly and permanently lower their high blood cholesterol levels caused by dietary challenge.

Abstract: Methods for treating neurological diseases and for testing Caloric Restriction (CR) mimetics or CR mimetic candidates. In one exemplary method, a CR mimetic candidate is administered to a transgenic animal and the effects of the administering are determined; the transgenic animal includes an added gene from another type of animal or a modified gene which is designed to produce a disease or ailment of the another type of animal, and the method seeks to determine whether the CR mimetic candidate improves the disease or ailment. Methods relating to neurological disease and other methods relating to CR mimetic testing are also described.

Abstract: The present invention relates to animal models of metabolic disorders such as obesity, diabetes, metabolic syndrome, insulin resistance, hyperinsulinemia, glucose intolerance, hyperlipidemia, and the like. In particular, the invention relates to transgenic non-human animals having a reduction in functional Jhdm2a gene expression and use of such animals and cells having reduced Jhdm2a expression in drug discovery. The invention further relates to the identification of subjects having or at increased risk for developing a metabolic disorder based on a genetic marker in the Jhdm2a gene.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO196, PRO217, PRO231, PRO236, PRO245, PRO246, PRO258, PRO287, PRO328, PRO344, PRO357, PRO526, PRO724, PRO731, PRO732, PRO1003, PRO1104, PRO1151, PRO1244, PRO1298, PRO1313, PRO1570, PRO1886, PRO1891, PRO4409, PRO5725, PRO5994, PRO6097, PRO7425, PRO10102, PRO10282, PRO61709 or PRO779 genes. Such in vivo studies and characterizations may provide valuable identification and discovery of therapeutics and/or treatments useful in the prevention, amelioration or correction of diseases or dysfunctions associated with gene disruptions such as neurological disorders; cardiovascular, endothelial or angiogenic disorders; eye abnormalities; immunological disorders; oncological disorders; bone metabolic abnormalities or disorders; lipid metabolic disorders; or developmental abnormalities.

Abstract: The present invention relates to a method of developing a Tumor Model System. The invention deals with a tumor model system with adhesion deprived cells. This observation provides a new method for primary detection of transformation of adhesion-deprived cells and tumorigenicity. The adhesion-deprived cells are capable of metastasizing at distant sites and the model system includes both the tumor formation and metastasis.

Abstract: The present invention provides methods of screening an agent for activity using teleosts. Methods of screening an agent for angiogenesis activity, toxic activity and an effect cell death activity in teleosts are provided. Methods of screening an agent for an activity in the brain or central nervous system in zebrafish are provided. The invention further provides high throughput methods of screening agents in multi-well plates.

Abstract: The present invention relates to a transgenic animal, which comprises in its genome a recombinant polynucleotide encoding one or more reporter proteins and a monocyte chemotactic protein-1 (MCP-1) promoter, wherein the one or more reporter proteins are expressed under the control of the MCP-1 promoter. A method for monitoring endogenous expression of MCP-1 in vivo is also provided, which is useful for identifying a regulator of the expression of MCP-1 or an anti-inflammatory agent.

Abstract: The present invention provides for a transgenic non-human animal whose cells contain a DNA sequence comprising: (a) a nerve tissue specific promoter; and (b) a DNA sequence which encodes a receptor for advanced glycation endproducts (RAGE), wherein the promoter and the DNA sequence which encodes the receptor for advanced glycation endproducts (RAGE) are operatively linked to each other and integrated in the genome of the non-human animal, and wherein said non-human animal exhibits a reduced amount of cerebral tissue infarcted following a transient middle cerebral artery occlusion compared to an identical non-human animal lacking said DNA sequence.

Abstract: The present invention provides for monitoring of NF-?B-associated inflammation in mice undergoing Id-driven autoimmune disease. The mice are triple transgenic mice expressing both Id+ B cells and Id-specific CD4+ T cells as well as a luciferase reporter transgene under NF-?B control. NF-?B activation and nuclear translocation of NF-?B, luciferase activity are repeatedly monitored in intact mice by whole body bioluminescence imaging. Results are corroborated at the cellular level by detection of luciferase protein expression in single cells. The results show that imaging of NF-?B activation permits early detection of subclinical disease as well as tracking of disease development.

Abstract: A method for controlling an electroporation apparatus for use in an animal such as human and a non-human animal, the method comprising a step of applying a voltage to an electrode of the electroporation apparatus placed in/on a biological sample of the animal in the presence of a nucleic acid construct capable of inhibiting the expression of a gene in the animal. In this manner, a nucleic acid construct can be introduced into a cell of a living body with good efficiency.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO194, PRO220, PRO241, PRO284, PRO331, PRO354, PRO355, PRO533, PRO541, PRO725, PRO937, PRO1014, PRO1120, PRO1182, PRO1325, PRO1382, PRO1410, PRO1555, PRO1556, PRO1760, PRO1787, PRO1868, PRO4326, PRO4332, PRO4346, PRO4400, PRO6003, PRO6094, PRO6244, PRO9820, PRO9828, PRO10274, PRO16090, PRO19644, PRO21340, PRO92165, PRO85143, PRO1124, PRO1026 or PRO23370 genes.

Abstract: This disclosure provides an intracellular fragment of natriuretic peptide receptor A (NPRA), referred to herein as soluble natriuretic peptide receptor-related fragment (sNRF). It is shown herein that sNRF causes NP resistance. Based on these observations, methods of treating a cardiovascular disorder by inhibiting the activity of sNRF are disclosed. Assays are provided that use sNRF to screen agents for their ability to increase the biological activity of an NPR, for example agents that increase the sensitivity of NPR for NPs (such as atrial natriuretic peptide, ANP), or that decrease growth factor deleterious effects, or combinations thereof. Also provided are agents identified using the disclosed assays, and methods of using the agents, for example to treat or diagnose a cardiovascular disorder, such as heart failure.

Abstract: The present invention relates to serine hydroxymethyltransferase (E.C. 2.1.2.1) as novel target for herbicides, and to nucleic acid sequences encoding a polypeptide with the biological activity of a serine hydroxymethyltransferase, which, when not present, bring about growth retardation symptoms and chlorotic leaves, comprising the nucleic acid sequence SEQ ID No:3, and functional equivalents of the abovementioned nucleic acid sequence or the nucleic acid sequence SEQ ID NO:7 and functional equivalents of the abovementioned nucleic acid sequence. Moreover, the present invention relates to the use of the abovementioned nucleic acid sequences, of functional analogs of the SEQ ID NO:3 or SEQ ID NO:7 or of polypeptides encoded by one of the abovementioned nucleic acid sequences in a method for identifying herbicidally active compounds which inhibit serine hydroxymethyltransferases, and to the use of these compounds which have been identified by the method as herbicides.

Abstract: Described is a method of screening for a therapeutic agent useful in the prophylaxis or treatment of AD comprising detecting oligomers of a peptide comprising an APP-G29xxxG33 motif in an assay system to which system a test compound has been added and comparing the size distribution of the oligomers of said peptide and/or degree of oligomerization with a control assay characterized by the absence of said test compound, wherein reduction of the amounts of dimers and/or tetramers indicates that said test compound might be suitable for prophylaxis or treatment of AD.

Abstract: The invention relates to a method for diagnosing pre-symptomatic metabolic syndrome in a subject, wherein said method comprises determining the expression level of a gene represented by a sequence selected from the group consisting of SEQ ID NO: 1-18 in a subject. The invention described target genes for preventing or stopping further progress of metabolic syndrome into clinical disease states.

Abstract: This invention relates to the finding that skin cancers, such as squamous cell carcinoma and basal cell carcinoma, are characterized by changes in the expression of specific microRNA molecules (miRNAs). These miRNAs may therefore be useful as biomarkers for skin cancers as well as therapeutic targets. Methods of diagnosis and treatment of skin cancers are provided, as well as methods of screening for therapeutic compounds.

Abstract: The present invention provides targets, methods, and reagents for the diagnosis and treatment of schizophrenia and related conditions. The invention provides methods for the diagnosis of schizophrenia and susceptibility to schizophrenia by detection of polymorphisms, mutations, variations, alterations in expression, etc., in calcineurin genes or calcineurin interacting genes, or polymorphisms linked to such genes. The invention provides oligonucleotides, arrays, and antibodies for detection of polymorphisms and variants. The invention provides transgenic mice having alterations in such genes. The invention also provides methods of treating schizophrenia by administering compounds that target these genes. The invention further provides screening methods for identifying such compounds and compounds obtained by performing the screens.

Abstract: The molecular mechanism underlying degenerative joint disease, also known as osteoarthritis (OA), is not fully understood. Disruption of mitogen inducible gene 6 (Mig-6) in mice by homologous recombination (KO mice) led to early onset OA as revealed by simultaneous enlargement and deformity of multiple joints, degradation of articular cartilage and the development of bony outgrowths or osteophytes within the joint space. The latter appeared to be derived from proliferation of mesenchymal progenitor cells followed by differentiation into chondrocytes. Because of the striking similarity to human OA, Mig-6 KO mice are a useful animal model for studying the mechanism of this disease and for testing new drugs or therapies for treating OA. These KO mice also developed epithelial hyperplasia, adenoma, and adenocarcinoma in organs such as lung, gallbladder, and bile duct. Mig-6 is therefore a tumor suppressor gene and is a candidate gene for the frequent Ip36 genetic alterations found in lung cancer.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO179, PRO181, PRO244, PRO247, PRO269, PRO293, PRO298, PRO339, PRO341, PRO347, PRO531, PRO537, PRO718, PRO773, PRO860, PRO871, PRO872, PRO813, PRO828, PRO1100, PRO1114, PRO115, PRO1126, PRO1133, PRO1154, PRO1185, PRO1194, PRO1287, PRO1291, PRO1293, PRO1310, PRO1312, PRO1335, PRO1339, PRO2155, PRO1356, PRO1385, PRO1412, PRO1487, PRO1758, PRO1779, PRO1785, PRO1889, PRO90318, PRO3434, PRO3579, PRO4322, PRO4343, PRO4347, PRO4403, PRO4976, PRO260, PRO6014, PRO6027, PRO6181, PRO6714, PRO9922, PRO7179, PRO7476, PRO9824, PRO19814, PRO19836, PRO20088, PRO70789, PRO50298, PRO51592, PRO1757, PRO4421, PRO9903, PRO1106, PRO1411, PRO1486, PRO1565, PRO4399 or PRO4404 genes.