Novel gene disruptions, compositions and methods relating thereto

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 PRO69122, PRO204, PRO214, PRO222, PRO234, PRO265, PRO309, PRO332, PRO342, PRO356, PRO540, PRO618, PRO944, PRO994, PRO1079, PRO1110, PRO1122, PRO1138, PRO1190, PRO1272, PRO1286, PRO1295, PRO1309, PRO1316, PRO1383, PRO1384, PRO1431, PRO1434, PRO1475, PRO1481, PRO1568, PRO1573, PRO1599, PRO1604, PRO1605, PRO1693, PRO1753, PRO1755, PRO1777, PRO1788, PRO1864, PRO1925, PRO1926, PRO3566, PRO4330, PRO4423, PRO36935, PRO4977, PRO4979, PRO4980, PRO4981, PRO5801, PRO5995, PRO6001, PRO6095, PRO6182, PRO7170, PRO7171, PRO7436, PRO9912, PRO9917, PRO37337, PRO37496, PRO19646, PRO21718, PRO19820, PRO21201, PRO20026, PRO20110, PRO23203 or PRO35250 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.

1 - 174 . (canceled) 
     
     
         175 . A method of identifying an agent that modulates a phenotype associated with a disruption of a gene which encodes for a PRO1079 polypeptide, the method comprising:
 (a) providing a non-human transgenic animal whose genome comprises a disruption of a gene which is an ortholog of a human gene that encodes for the PRO1079 polypeptide;   (b) measuring a physiological characteristic of the non-human transgenic animal of (a);   (c) comparing the measured physiological characteristic of (b) with that of a gender matched wild-type animal, wherein the physiological characteristic of the non-human transgenic animal that differs from the physiological characteristic of the wild-type animal is identified as a phenotype resulting from the gene disruption in the non-human transgenic animal;   (d) administering a test agent to the non-human transgenic animal of (a); and   (e) determining whether the test agent modulates the identified phenotype associated with gene disruption in the non-human transgenic animal.   
     
     
         176 . The method of  claim 175 , wherein the phenotype associated with the gene disruption comprises a neurological disorder; a cardiovascular, endothelial or angiogenic disorder; an eye abnormality; an immunological disorder; an oncological disorder; a bone metabolic abnormality or disorder; a lipid metabolic disorder; or a developmental abnormality. 
     
     
         177 . The method of  claim 176 , wherein the neurological disorder is an increased anxiety-like response during open field activity testing. 
     
     
         178 . The method of  claim 176 , wherein the neurological disorder is a decreased anxiety-like response during open field activity testing. 
     
     
         179 . The method of  claim 176 , wherein the neurological disorder is an abnormal circadian rhythm during home-cage activity testing. 
     
     
         180 . The method of  claim 176 , wherein the neurological disorder is an enhanced motor coordination during inverted screen testing. 
     
     
         181 . The method of  claim 176 , wherein the neurological disorder is an impaired motor coordination during inverted screen testing. 
     
     
         182 . The method of  claim 176 , wherein the neurological disorder is depression, generalized anxiety disorders, attention deficit disorder, sleep disorder, hyperactivity disorder, obsessive compulsive disorder, schizophrenia, cognitive disorders, hyperalgesia or sensory disorders. 
     
     
         183 . The method of  claim 176 , wherein the eye abnormality is a retinal abnormality. 
     
     
         184 . The method of  claim 176 , wherein the eye abnormality is consistent with vision problems or blindness. 
     
     
         185 . The method of  claim 183 , wherein the retinal abnormality is consistent with retinitis pigmentosa. 
     
     
         186 . The method of  claim 183 , wherein the retinal abnormality is characterized by retinal degeneration or retinal dysplasia. 
     
     
         187 . The method of  claim 183 , wherein the retinal abnormality is consistent with retinal dysplasia, various retinopathies, including retinopathy of prematurity, retrolental fibroplasia, neovascular glaucoma, age-related macular degeneration, diabetic macular edema, corneal neovascularization, corneal graft neovascularization, corneal graft rejection, retinal/choroidal neovascularization, neovascularization of the angle (rubeosis), ocular neovascular disease, vascular restenosis, arteriovenous malformations (AVM), meningioma, hemangioma, angiofibroma, thyroid hyperplasias (including Grave's disease), corneal and other tissue transplantation, retinal artery obstruction or occlusion; retinal degeneration causing secondary atrophy of the retinal vasculature, retinitis pigmentosa, macular dystrophies, Stargardt's disease, congenital stationary night blindness, choroideremia, gyrate atrophy, Leber's congenital amaurosis, retinoschisis disorders, Wagner's syndrome, Usher syndromes, Zellweger syndrome, Saldino-Mainzer syndrome, Senior-Loken syndrome, Bardet-Biedl syndrome, Alport's syndrome, Alstrom's syndrome, Cockayne's syndrome, dysplaisa spondyloepiphysaria congentia, Flynn-Aird syndrome, Friedreich ataxia, Hallgren syndrome, Marshall syndrome, Albers-Schnoberg disease, Refsum's disease, Kearns-Sayre syndrome, Waardenburg's syndrome, Alagile syndrome, myotonic dystrophy, olivopontocerebellar atrophy, Pierre-Marie dunsdrome, Stickler syndrome, carotinemeia, cystinosis, Wolfram syndrome, Bassen-Kornzweig syndrome, abetalipoproteinemia, incontinentia pigmenti, Batten's disease, mucopolysaccharidoses, homocystinuria, or mannosidosis. 
     
     
         188 . The method of  claim 176 , wherein the eye abnormality is a cataract. 
     
     
         189 . The method of  claim 188 , wherein the cataract is consistent with systemic diseases such as human Down's syndrome, Hallerman-Streiff syndrome, Lowe syndrome, galactosemia, Marfan syndrome, Trismoy 13-15, Alport syndrome, myotonic dystrophy, Fabry disease, hypoparathroidism or Conradi syndrome. 
     
     
         190 . The method of  claim 176 , wherein the developmental abnormality comprises embryonic lethality or reduced viability. 
     
     
         191 . The method of  claim 176 , wherein the cardiovascular, endothelial or angiogenic disorders are arterial diseases, such as diabetes mellitus; papilledema; optic atrophy; atherosclerosis; angina; myocardial infarctions such as acute myocardial infarctions, cardiac hypertrophy, and heart failure such as congestive heart failure; hypertension; inflammatory vasculitides; Reynaud's disease and Reynaud's phenomenon; aneurysms and arterial restenosis; venous and lymphatic disorders such as thrombophlebitis, lymphangitis, and lymphedema; peripheral vascular disease; cancer such as vascular tumors, e.g., hemangioma (capillary and cavernous), glomus tumors, telangiectasia, bacillary angiomatosis, hemangioendothelioma, angiosarcoma, haemangiopericytoma, Kaposi's sarcoma, lymphangioma, and lymphangiosarcoma; tumor angiogenesis; trauma such as wounds, burns, and other injured tissue, implant fixation, scarring; ischemia reperfusion injury; rheumatoid arthritis; cerebrovascular disease; renal diseases such as acute renal failure, or osteoporosis. 
     
     
         192 . The method of  claim 176 , wherein the immunological disorders are systemic lupus erythematosis; rheumatoid arthritis; juvenile chronic arthritis spondyloarthropathies; systemic sclerosis (scleroderma); idiopathic inflammatory myopathies (dermatomyositis, polymyositis); Sjogren's syndrome; systemic vasculitis; sarcoidosis; autoimmune hemolytic anemia (immune pancytopenia, paroxysmal nocturnal hemoglobinuria); autoimmune thrombocytopenia (idiopathic thrombocytopenic purpura, immune-mediated thrombocytopenia); thyroiditis (Grave's disease, Hashimoto's thyroiditis, juvenile lymphocytic thyroiditis, atrophic thyroiditis); diabetes mellitus; immune-mediated renal disease (glomerulonephritis, tubulointerstitial nephritis); demyelinating diseases of the central and peripheral nervous systems such as multiple sclerosis, idiopathic demyelinating polyneuropathy or Guillain-Barre syndrome, and chronic inflammatory demyelinating polyneuropathy; hepatobiliary diseases such as infectious hepatitis (hepatitis A, B, C, D, E and other non-hepatotropic viruses), autoimmune chronic active hepatitis, primary biliary cirrhosis, granulomatous hepatitis, and sclerosing cholangitis; inflammatory bowel disease (ulcerative colitis: Crohn's disease); gluten-sensitive enteropathy, and Whipple's disease; autoimmune or immune-mediated skin diseases including bullous skin diseases, erythema multiforme and contact dermatitis, psoriasis; allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, food hypersensitivity and urticaria; immunologic diseases of the lung such as eosinophilic pneumonia, idiopathic pulmonary fibrosis and hypersensitivity pneumonitis; or transplantation-associated diseases including graft rejection and graft-versus-host disease. 
     
     
         193 . The method of  claim 176 , wherein said bone metabolic abnormality or disorder is arthritis, osteoporosis or osteopetrosis. 
     
     
         194 . The method of  claim 175 , wherein the non-human transgenic animal exhibits at least one of the following physiological characteristics compared with gender matched wild-type littermates: increased anxiety-like response during open field testing; decreased anxiety during open field testing; hypoactivity with no circadian rhythm; increased total distance traveled during open field testing (hyperactivity); decreased locomotor activity during open field testing; abnormal circadiian rhythm during home-cage activity testing (low activity during the light phase); abnormal circadian rhythm during home-cage activity testing including decreased ambulatory counts; abnormal circadian rhythm during home-cage activity testing including increased ambulatory counts; whiskers absent due to anxiety phenotype; enhanced circadian rhythm; increased stress induced hyperthermia with increased stress response (increased anxiety); increased resistance to stress induced hyperthermia; decreased resistance to stress induced hyperthermia; enhanced motor coordination during inverted screen testing; impaired motor coordination during inverted screen testing; increased immobility in tail suspension (increased depressive-like response); increased depressive-like response during tail suspension testing; decreased depressive-like response during tail suspension testing; clutched hind limbs during tail suspension testing; decreased startle response during prepulse inhibition testing; no startle response indicating deafness; increased prepulse inhibition with enhanced sensorimotor gating/attention; increased latency on hotplate indicative of decreased sensitivity to heat-induced pain; opthamological abnormalities; corneal epidermidalization of the corneal stroma with scarring and blocked vision; metaplasia of the cornea and sclera; attenuated retinal arteries; retinal hemorrhage; optic nerve abnormalities; dilated optic disc; increased intraocular pressure; corneal epithelialization with underdeveloped eyelids; retinal degeneration; agenesis of the Harderian gland; retinal vessel disorganization, microaneurysms and retinal capillary leakage; impaired vision; decreased heart rate; decreased mean systolic blood pressure; increased mean systolic blood pressure; increased insulin sensitivity; increased mean fasting serum glucose levels; decreased mean serum glucose levels; increased mean serum cholesterol levels; decreased mean serum cholesterol levels; increased mean serum triglyceride levels; enhanced glucose tolerance; impaired glucose tolerance; decreased mean serum insulin levels; ketonemia; decreased mean serum calcium; blood urobilinogen, nitrites, protein and ketones; decreased sodium and chloride; increased bilirubin; notable lipemia; increased uric acid and potassium levels; increased mean serum alkaline phosphatase levels; decreased mean serum alkaline phosphatase levels; blood in the urine; glucosuria; increased nitrituria; ketonuria; increased mean percentage of natural killer cells; decreased mean percentage of natural killer cells; abnormal leukocyte count; leukopenia due to lymphopenia and granulocytopenia; increased mean percentage of CD4 cells; decreased mean percentage of CD4 cells; decreased mean percentage of CD8 cells; reduced percentage of naive CD4 and CD8 T cells in lymph nodes; increased mean percentage of B cells in peripheral blood; decrease total white blood cells and lymphocyte counts; decreased absolute lymphocyte counts; increased mean absolute monocyte count; increased mean absolute neutrophil count; decreased in mean serum IgA levels; increase in mean serum IgA levels; increase in IgG1 levels; decreased mean serum IgG1 levels; decreased mean serum IgG1, IgG3, IgG2b and IgG2a levels; decreased mean serum IgG2a levels; decreased mean serum IgG2b levels; decreased mean serum IgG3 and IgM levels; increase in mean serum IgG2a levels; increase in mean serum IgG1, IgG2a and IgG3 levels; increase in mean serum IgG3 levels; anemia; decreased red blood cell count, decreased hemoglobin and decreased hematocrit with increased mean red blood cell count; increased mean corpuscular volume; decreased mean corpuscular volume; decreased mean corpuscular hemoglobin; increased red blood cell distribution width; defect in erythropoiesis; increased IgM+ IgD+ and B220hi/CD43− cells in bone marrow; decreased percentage of B220hi/CD43− IgM+ IgD+ cells in bone marrow; increased percentage of TCRB+ cells in Peyer's patches; reduction in naive T cells (especially CD4) in lymph nodes; increased percentage of CD11b+CD11c− cells (monocytes) in spleen; increased percentage of IgM+, CD117+ cells in bone marrow, higher percentage of dead B cells, decreased B cells, increased CD4 and CD8 T cells in lymph; B cells increased in bone marrow and significantly decreased in lymph node; notably decreased CD21hiCD23med B cells in spleen; decrease in Peyer's patch B220+ cells; decreased mean percentages of CD8 and natural killer cells with increased mean percentage of B cells; reduced number of TCRB+CD38+ activated T cells in Peyer's patches; decreased mean percentage of CD4 cells with increased mean percentage of B cells; decreased B220+ CD38low and IgM in Payer's patches; increased mean platelet count; decreased mean platelet count; widespread apoptosis and loss of T lymphocytes in the thymic cortex and depletion of T cells in spleen; increased mean serum IgG2a response to an ovalbumin challenge; decreased to no serum IgG1 and IgG2a response to ovalbumin challenge; increased mean serum IgG1 response to an ovalbumin challenge; decreased mean serum TNF-alpha, MCP-1 and IL-6 responses to LPS challenge; increased mean serum MCP-1 response to a LPS challenge; increased mean serum TNF-alpha response to a LPS challenge; increased mean serum IL-6 response to a LPS challenge; increased skin fibroblast proliferation; decreased skin fibroblast proliferation; increased mean percent of total body fat and total fat mass; increased mean body weight; increased mean body length; increased total tissue mass (TTM); increased lean body mass (LBM); increased femoral bone mineral density (BMD); increased vertebral bone mineral density (BMD); increased bone mineral density (BMD); increased total body volumetric bone mineral density (vBMD); increased bone mineral content (BMC); increased mean femoral midshaft cortical thickness and cross-sectional area; increased mean vertebral trabecular bone volume, number and connectivity density; decreased mean percent of total body fat and total fat mass; decreased mean body weight; decreased mean body length; decreased total tissue mass (TTM); decreased lean body mass (LBM); decreased femoral bone mineral density (BMD); decreased vertebral bone mineral density (BMD); decreased bone mineral density (BMD); decreased bone mineral content (BMC); decreased bone mineral density index; decreased volumetric bone mineral density (vBMD); decreased mean femoral midshaft cortical thickness and cross-sectional area; decreased mean vertebral trabecular bone volume, number and connectivity density; marked osteopetrosis with increased bone mineralization; chronic inflammation in various tissues; thymic atrophy; systemic histiocytic storage disease affecting macrophages in liver, spleen and mesenteric lymph nodes; reduced liver size; chronic active hepatitis with focal hepatocyte necrosis; fatty changes in the liver; increased intracytoplasmic vacuolization of glycogen in hepatocytes; pancreatic dyserythropoietic anemia (type 1); multifocal neuronal necrosis; diffuse abiotrophy of the cerebellum granule cell layer; multifocal developmental malformation of the brain; hydronephosis; diffuse alopecia; epidermal hyperkeratosis; hypochromasia and anisocytosis characterized by abnormal erythrocytes (abnormally low hemoglobin and decreased erythropoiesis); growth retardation; development abnormalities; granulocytic hypoplasia of bone marrow; decreased numbers of myeloid granulocytic cell precursors; decreased granulocytopoiesis; no teeth; stunted growth with general reduction in all organ size; myocardial defects with defective structure and arrangement of the cardiac myocytes; cardiomyopathy with condensed eosinophilic sarcoplasm; congestive heart failure; pancreatic islets of Langerhans smaller and distribution of alpha (glycogen) and beta (insulin) cells altered; notable histopathologic alteration in cytoplasm of all cells in the zona fasciculata of the adrenal gland consistent with altered lipid/cholesterol uptake or metabolism (elevated cholesterol and triglycerides); infertility; testicular degeneration; vacuolar degeneration of seminiferous tubules; hypospermia; atrophic testes; ovarian and uterine hypoplasia; mammary gland was represented with just a few ducts; growth retardation with reduced viability; and embryonic lethality. 
     
     
         195 - 198 . (canceled) 
     
     
         199 . A method of identifying an agent that modulates a physiological characteristic associated with a disruption of a gene which encodes for a PRO1079 polypeptide, the method comprising:
 (a) providing a non-human transgenic animal whose genome comprises a disruption of a gene which is an ortholog of a human gene that encodes for a PRO1079 polypeptide;   (b) measuring a physiological characteristic exhibited by the non-human transgenic animal of (a);   (c) comparing the measured physiological characteristic of (b) with that of a gender matched wild-type animal, wherein the physiological characteristic exhibited by the non-human transgenic animal that differs from the physiological characteristic exhibited by the wild-type animal is identified as a physiological characteristic associated with gene disruption;   (d) administering a test agent to the non-human transgenic animal of (a); and   (e) determining whether the physiological characteristic associated with gene disruption is modulated.   
     
     
         200 . The method of  claim 199 , wherein the non-human transgenic animal exhibits at least one of the following physiological characteristics during open field testing; decreased anxiety during open field testing; hypoactivity with no circadian rhythm; increased total distance traveled during open field testing (hyperactivity); decreased locomotor activity during open field testing; abnormal circadian rhythm during home-cage activity testing (low activity during the light phase); abnormal circadian rhythm during home-cage activity testing including decreased ambulatory counts; abnormal circadian rhythm during home-cage activity testing including increased ambulatory counts; whiskers absent due to anxiety phenotype; enhanced circadian rhythm; increased stress induced hyperthermia with increased stress response (increased anxiety); increased resistance to stress induced hyperthermia; decreased resistance to stress induced hyperthermia; enhanced motor coordination during inverted screen testing; impaired motor coordination during inverted screen testing; increased immobility in tail suspension (increased depressive-like response); increased depressive-like response during tail suspension testing; decreased depressive-like response during tail suspension testing; clutched hind limbs during tail suspension testing; decreased startle response during prepulse inhibition testing; no startle response indicating deafness; increased prepulse inhibition with enhanced sensorimotor gating/attention; increased latency on hotplate indicative of decreased sensitivity to heat-induced pain; opthamological abnormalities; corneal epidermidalization of the corneal stroma with scarring and blocked vision; metaplasia of the cornea and sclera; attenuated retinal arteries; retinal hemorrhage; optic nerve abnormalities; dilated optic disc; increased intraocular pressure; corneal epithelialization with underdeveloped eyelids; retinal degeneration; agenesis of the Harderian gland; retinal vessel disorganization, microaneurysms and retinal capillary leakage; impaired vision; decreased heart rate; decreased mean systolic blood pressure; increased mean systolic blood pressure; increased insulin sensitivity; increased mean fasting serum glucose levels; decreased mean serum glucose levels; increased mean serum cholesterol levels; decreased mean serum cholesterol levels; increased mean serum triglyceride levels; enhanced glucose tolerance; impaired glucose tolerance; decreased mean serum insulin levels; ketonemia; decreased mean serum calcium; blood urobilinogen, nitrites, protein and ketones; decreased sodium and chloride; increased bilirubin; notable lipemia; increased uric acid and potassium levels; increased mean serum alkaline phosphatase levels; decreased mean serum alkaline phosphatase levels; blood in the urine; glucosuria; increased nitrituria; ketonuria; increased mean percentage of natural killer cells; decreased mean percentage of natural killer cells; abnormal leukocyte count; leukopenia due to lymphopenia and granulocytopenia; increased mean percentage of CD4 cells; decreased mean percentage of CD4 cells; decreased mean percentage of CD8 cells; reduced percentage of naive CD4 and CD8 T cells in lymph nodes; increased mean percentage of B cells in peripheral blood; decrease total white blood cells and lymphocyte counts; decreased absolute lymphocyte counts; increased mean absolute monocyte count; increased mean absolute neutrophil count; decreased in mean serum IgA levels; increase in mean serum IgA levels; increase in IgG1 levels; decreased mean serum IgG1 levels; decreased mean serum IgG1, IgG3, IgG2b and IgG2a levels; decreased mean serum IgG2a levels; decreased mean serum IgG2b levels; decreased mean serum IgG3 and IgM levels; increase in mean serum IgG2a levels; increase in mean serum IgG1, IgG2a and IgG3 levels; increase in mean serum IgG3 levels; anemia; decreased red blood cell count, decreased hemoglobin and decreased hematocrit with increased mean red blood cell count; increased mean corpuscular volume; decreased mean corpuscular volume; decreased mean corpuscular hemoglobin; increased red blood cell distribution width; defect in erythropoiesis; increased IgM+ IgD+ and B220hi/CD43− cells in bone marrow; decreased percentage of B220hi/CD43− IgM+ IgD+ cells in bone marrow; increased percentage of TCRB+ cells in Peyer's patches; reduction in naive T cells (especially CD4) in lymph nodes; increased percentage of CD11b+CD11c− cells (monocytes) in spleen; increased percentage of IgM+, CD117+ cells in bone marrow, higher percentage of dead B cells, decreased B cells, increased CD4 and CD8 T cells in lymph; B cells increased in bone marrow and significantly decreased in lymph node; notably decreased CD21hiCD23med B cells in spleen; decrease in Peyer's patch B220+ cells; decreased mean percentages of CD8 and natural killer cells with increased mean percentage of B cells; reduced number of TCRB+ CD38+ activated T cells in Peyer's patches; decreased mean percentage of CD4 cells with increased mean percentage of B cells; decreased B220+ CD38low and IgM in Payer's patches; increased mean platelet count; decreased mean platelet count; widespread apoptosis and loss of T lymphocytes in the thymic cortex and depletion of T cells in spleen; increased mean serum IgG2a response to an ovalbumin challenge; decreased to no serum IgG1 and IgG2a response to ovalbumin challenge; increased mean serum IgG1 response to an ovalbumin challenge; decreased mean serum TNF-alpha, MCP-1 and IL-6 responses to LPS challenge; increased mean serum MCP-1 response to a LPS challenge; increased mean serum TNF-alpha response to a LPS challenge; increased mean serum IL-6 response to a LPS challenge; increased skin fibroblast proliferation; decreased skin fibroblast proliferation; increased mean percent of total body fat and total fat mass; increased mean body weight; increased mean body length; increased total tissue mass (TTM); increased lean body mass (LBM); increased femoral bone mineral density (BMD); increased vertebral bone mineral density (BMD); increased bone mineral density (BMD); increased total body volumetric bone mineral density (vBMD); increased bone mineral content (BMC); increased mean femoral midshaft cortical thickness and cross-sectional area; increased mean vertebral trabecular bone volume, number and connectivity density; decreased mean percent of total body fat and total fat mass; decreased mean body weight; decreased mean body length; decreased total tissue mass (TTM); decreased lean body mass (LBM); decreased femoral bone mineral density (BMD); decreased vertebral bone mineral density (BMD); decreased bone mineral density (BMD); decreased bone mineral content (BMC); decreased bone mineral density index; decreased volumetric bone mineral density (vBMD); decreased mean femoral midshaft cortical thickness and cross-sectional area; decreased mean vertebral trabecular bone volume, number and connectivity density; marked osteopetrosis with increased bone mineralization; chronic inflammation in various tissues; thymic atrophy; systemic histiocytic storage disease affecting macrophages in liver, spleen and mesenteric lymph nodes; reduced liver size; chronic active hepatitis with focal hepatocyte necrosis; fatty changes in the liver; increased intracytoplasmic vacuolization of glycogen in hepatocytes; pancreatic dyserythropoietic anemia (type 1); multifocal neuronal necrosis; diffuse abiotrophy of the cerebellum granule cell layer; multifocal developmental malformation of the brain; hydronephosis; diffuse alopecia; epidermal hyperkeratosis; hypochromasia and anisocytosis characterized by abnormal erythrocytes (abnormally low hemoglobin and decreased erythropoiesis); growth retardation; development abnormalities; granulocytic hypoplasia of bone marrow; decreased numbers of myeloid granulocytic cell precursors; decreased granulocytopoiesis; no teeth; stunted growth with general reduction in all organ size; myocardial defects with defective structure and arrangement of the cardiac myocytes; cardiomyopathy with condensed eosinophilic sarcoplasm; congestive heart failure; pancreatic islets of Langerhans smaller and distribution of alpha (glycogen) and beta (insulin) cells altered; notable histopathologic alteration in cytoplasm of all cells in the zona fasciculata of the adrenal gland consistent with altered lipid/cholesterol uptake or metabolism (elevated cholesterol and triglycerides); infertility; testicular degeneration; vacuolar degeneration of seminiferous tubules; hypospermia; atrophic testes; ovarian and uterine hypoplasia; mammary gland was represented with just a few ducts; growth retardation with reduced viability; and embryonic lethality. 
     
     
         201 - 204 . (canceled) 
     
     
         205 . A method of identifying an agent which modulates a behavior associated with a disruption of a gene which encodes for a PRO1079 polypeptide, the method comprising:
 (a) providing a non-human transgenic animal whose genome comprises a disruption of a gene which is an ortholog of a human gene that encodes for a PRO1079 polypeptide;   (b) observing the behavior exhibited by the non-human transgenic animal of (a);   (c) comparing the observed behavior of (b) with that of a gender matched wild-type animal, wherein the observed behavior exhibited by the non-human transgenic animal that differs from the observed behavior exhibited by the wild-type animal is identified as a behavior associated with gene disruption;   (d) administering a test agent to the non-human transgenic animal of (a); and   (e) determining whether the agent modulates the behavior associated with gene disruption.   
     
     
         206 . The method of  claim 205 , wherein the behavior is an increased anxiety-like response during open field activity testing. 
     
     
         207 . The method of  claim 205 , wherein the behavior is a decreased anxiety-like response during open field activity testing. 
     
     
         208 . The method of  claim 205 , wherein the behavior is an abnormal circadian rhythm during home-cage activity testing. 
     
     
         209 . The method of  claim 205 , wherein the behavior is an enhanced motor coordination during inverted screen testing. 
     
     
         210 . The method of  claim 205 , wherein the behavior is an impaired motor coordination during inverted screen testing. 
     
     
         211 . The method of  claim 205 , wherein the behavior is depression, generalized anxiety disorders, attention deficit disorder, sleep disorder, hyperactivity disorder, obsessive compulsive disorder, schizophrenia, cognitive disorders, hyperalgesia or sensory disorders. 
     
     
         212 - 289 . (canceled)