Nova Patents
EP1995321A2

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 PRO226, PRO257, PRO268, PRO290, PRO36006, PRO363, PRO365, PRO382, PRO444, PRO705, PRO1071, PRO112 PRO1134 PRO115 PRO1281 PRO1343 PRO1379 PRO1380 PRO1387 PRO1419 PRO1433, PRO1474, PRO1550, PRO1571, PRO1572, PRO1759, PRO1904, PRO35193, PRO4341, 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. 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.

EP1995321A2, drawing sheet 1
Sheet 1 of 295

Term

Term ended

Projected expiry passed 18 July 2026, 0.2 years ago.

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18 claims: 9 independent, 9 dependent

  1. 1
    A method of identifying a phenotype associated with a disruption of a gene which encodes for a PRO10196 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 PRO10196 polypeptide;(b) measuring a physiological characteristic of the non-human transgenic animal;and (c) comparing the measured physiological characteristic 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.
  2. 2
    The method of Claim 1, wherein the non-human transgenic animal is heterozygous for the disruption of a gene which encodes for a PRO10196 polypeptide.
  3. 3
    A method of identifying an agent that modulates a phenotype associated with a disruption of a gene which encodes for a PRO10196 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 PRO10196 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.
  4. 4
    A method of identifying an agent that modulates a physiological characteristic associated with a disruption of a gene which encodes for a PRO10196 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 PRO10196 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.
  5. 5
    The method of Claim 1 or Claim 3, wherein the phenotype exhibited by the non-human transgenic animal as compared with gender matched wild-type littermates is at least one of the following:a cardiovascular or lipid metabolic disorder.
  6. 6
    A method of identifying an agent that ameliorates or modulates a cardiovascular or lipid metabolic disorder associated with a disruption in a gene which encodes for a PRO10196 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 PRO10196 polypeptide;(b) administering a test agent to said non-human transgenic animal;and (c) determining whether said test agent ameliorates or modulates the cardiovascular or lipid metabolic disorder in the non-human transgenic animal.
  7. 7
    The method of any one of Claims 1, 3, 4 and 6, wherein the non-human transgenic animal exhibits at least one of the following physiological characteristics compared with gender matched wild-type littermates:increased mean serum glucose levels;increased mean serum cholesterol levels;and increased total tissue mass (TTM) and total body fat (% and g).
  8. 8
    A method of identifying an agent that modulates the expression of a PRO10196 polypeptide, the method comprising:(a) contacting a test agent with a host cell expressing a PRO10196 polypeptide;and (b) determining whether the test agent modulates the expression of the PRO10196 polypeptide by the host cell.
  9. 9
    A method of evaluating a therapeutic agent capable of affecting a condition associated with a disruption of a gene which encodes for a PRO10196 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 PRO10196 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.
  10. 10
    The method of Claim 9, wherein the condition is a cardiovascular or lipid metabolic disorder.
  11. 11
    A method of identifying an agent that ameliorates or modulates a cardiovascular or lipid metabolic disorder associated with a disruption in the gene which encodes for a PRO10196 polypeptide, the method comprising:(a) providing a non-human transgenic animal cell culture, each cell of said culture comprising a disruption of the gene which encodes for a PRO10196 polypeptide;(b) administering a test agent to said cell culture;and (c) determining whether said test agent ameliorates or modulates the cardiovascular or lipid metabolic disorder in said cell culture.
  12. 12
    An isolated cell derived from 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 PRO10196 polypeptide, preferably a murine cell, more preferably a murine cell embryonic stem cell.
  13. 13
    The isolated cell of Claim 12, wherein the non-human transgenic animal exhibits at least one of the following phenotypes compared with gender matched wild-type littermates:a cardiovascular or lipid metabolic disorder.
  14. 14
    An agent identified by the method of any one of Claims 3, 4, 6, 8 and 11 or a therapeutic agent identified by the method of Claim 9.
  15. 15
    The agent or therapeutic agent of Claim 14 which is an agonist or antagonist of a PRO10196 polypeptide, preferably wherein the agonist or antagonist is an anti-PRO10196 antibody.
  16. 16
    A therapeutic agent identified by the method of Claim 6 or Claim 9.
  17. 17
    A pharmaceutical composition comprising the therapeutic agent of Claim 14.
  18. 18
    A method of (i) treating or preventing or ameliorating a cardiovascular or lipid metabolic disorder , the method comprising administering to a subject in need of such treatment whom may already have the disorder, or may be prone to have the disorder or may be in whom the disorder is to be prevented, a therapeutically effective amount of the agonist antibody of Claim 15 as dependent from Claim 8, or agonists or antagonists thereof, thereby effectively treating or preventing or ameliorating said disorder;(ii) modulating a phenotype associated with a disruption of a gene which encodes for a PRO10196 polypeptide, the method comprising administering to a subject whom may already have the phenotype, or may be prone to have the phenotype or may be in whom the phenotype is to be prevented, an effective amount of the agent of Claim 14 as dependent from Claim 3, or agonists or antagonists thereof, thereby effectively modulating the phenotype;(iii) modulating a physiological characteristic associated with a disruption of a gene which encodes for a PRO10196 polypeptide, the method comprising administering to a subject whom may already exhibit the physiological characteristic, or may be prone to exhibit the physiological characteristic or may be in whom the physiological characteristic is to be prevented, an effective amount of the agent of Claim 14 as dependent from Claim 4, or agonists or antagonists thereof, thereby effectively modulating the physiological characteristic;(iv) modulating the expression of a PRO10196 polypeptide, the method comprising administering to a host cell expressing said PRO10196 polypeptide, an effective amount of the agent of Claim 14 as dependent from Claim 8, or agonists or antagonists thereof, thereby effectively modulating the expression of said polypeptide;(v) modulating a condition associated with a disruption of a gene which encodes for a PRO10196 polypeptide, the method comprising administering to a subject whom may have the condition, or may be prone to have the condition or may be in whom the condition is to be prevented, a therapeutically effective amount of the therapeutic agent of Claim 14 as dependent from Claim 9, or agonists or antagonists thereof, thereby effectively modulating the condition;(vi) treating or preventing or ameliorating a cardiovascular disorder associated with the disruption of a gene which encodes for a PRO10196 polypeptide, the method comprising administering to a non-human transgenic animal cell culture, each cell of said culture comprising a disruption of the gene which encodes for a PRO10196 polypeptide, a therapeutically effective amount of the agent of Claim 14 as dependent from Claim 11, or agonists or antagonists thereof, thereby effectively treating or preventing or ameliorating said disorder.
Independent claims18