Novel Gene Disruptions, Compositions and Methods Relating Thereto

A method of identifying an agent that modulates a phenotype associated with a disruption of a gene which encodes for a 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 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 PRO218, PRO228, PRO271, PRO273, PRO295, PRO302, PRO305, PRO326, PRO386, PRO655, PRO162, PRO788, PRO792, PRO940, PRO941, PRO1004, PRO112, 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 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.

A method of identifying an agent that modulates a physiological characteristic associated with a disruption of a gene which encodes for a 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 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 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 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.

A method of identifying an agent which modulates a behavior associated with a disruption of a gene which encodes for a 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 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 PRO218, PRO228, PRO271, PRO273, PRO295, PRO302, PRO305, PRO326, PRO386, PRO655, PRO162, PRO788, PRO792, PRO940, PRO941, PRO1004, PRO112, 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 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.

A method of identifying an agent that ameliorates or modulates 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 associated with a disruption in a gene which encodes for a 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 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 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 polypeptide;
• (b) administering a test agent to said non-human transgenic animal;
• and
• (c) determining whether said test agent ameliorates or modulates the neurological disorder;
• cardiovascular, endothelial or angiogenic disorder;
• eye abnormality;
• immunological disorder;
• oncological disorder;
• bone metabolic abnormality or disorder;
• lipid metabolic disorder;
• or developmental abnormality in the non-human transgenic animal.

A method of identifying an agent that modulates the expression of a 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 polypeptide, the method comprising:

• (a) contacting a test agent with a host cell expressing a 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 polypeptide;
• and
• (b) determining whether the test agent modulates the expression of the 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 polypeptide by the host cell.

A method of evaluating a therapeutic agent capable of affecting a condition associated with a disruption of a gene which encodes for a 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 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 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 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 condition 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) evaluating the effects of the test agent on the identified condition associated with gene disruption in the non-human transgenic animal.

A method of identifying an agent that mimics a condition or phenotype associated with a disruption in a gene which encodes a 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 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 a 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 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 gender matched wild-type animal is identified as a condition or phenotype resulting from the gene disruption in the non-human transgenic animal;
• (d) administering a test agent to said gender matched wild-type animal;
• and
• (e) determining whether said test agent mimics the condition or phenotype initially observed in the non-human transgenic animal.

A method of evaluating a therapeutic agent capable of mimicking a condition or phenotype associated with a disruption of a gene which encodes a 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 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 a 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 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 gender matched wild-type animal is identified as a condition or phenotype resulting from the gene disruption in the non-human transgenic animal;
• (d) administering a test agent to said gender matched wild-type animal of (c);
• and
• (e) evaluating the ability of the test agent to mimic the condition or phenotype associated with gene disruption in the non-human transgenic animal.