Claims
- 1. A targeting construct comprising:
(a) a first polynucleotide sequence homologous to a anaphylatoxin C3a receptor gene; (b) a second polynucleotide sequence homologous to the anaphylatoxin C3a receptor gene; and (c) a selectable marker.
- 2. The targeting construct of claim 1, wherein the targeting construct further comprises a screening marker.
- 3. A method of producing a targeting construct, the method comprising:
(a) providing a first polynucleotide sequence homologous to a anaphylatoxin C3a receptor gene; (b) providing a second polynucleotide sequence homologous to the anaphylatoxin C3a receptor; (c) providing a selectable marker; and (d) inserting the first sequence, second sequence, and selectable marker into a vector, to produce the targeting construct.
- 4. A method of producing a targeting construct, the method comprising:
(a) providing a polynucleotide comprising a first sequence homologous to a first region of a anaphylatoxin C3a receptor gene and a second sequence homologous to a second receptor of an anaphylatoxin C3a receptor gene; (b) inserting a positive selection marker in between the first and second sequences to form the targeting construct.
- 5. A cell comprising a disruption in an anaphylatoxin C3a receptor gene.
- 6. The cell of claim 5, wherein the cell is a murine cell.
- 7. The cell of claim 6, wherein the murine cell is an embryonic stem cell.
- 8. A non-human transgenic animal comprising a disruption in an anaphylatoxin C3a receptor gene.
- 9. A cell derived from the non-human transgenic animal of claim 8.
- 10. A method of producing a transgenic mouse comprising a disruption in a anaphylatoxin C3a receptor gene, the method comprising:
(a) introducing the targeting construct of claim 1 into a cell; (b) introducing the cell into a blastocyst; (c) implanting the resulting blastocyst into a pseudopregnant mouse, wherein said pseudopregnant mouse gives birth to a chimeric mouse; and (d) breeding the chimeric mouse to produce the transgenic mouse.
- 11. A method of identifying an agent that modulates the expression of a anaphylatoxin C3a receptor, the method comprising:
(a) providing a non-human transgenic animal comprising a disruption in a anaphylatoxin C3a receptor gene; (b) administering an agent to the non-human transgenic animal; and (c) determining whether the expression of anaphylatoxin C3a receptor in the non-human transgenic animal is modulated.
- 12. A method of identifying an agent that modulates the function of a anaphylatoxin C3a receptor, the method comprising:
(a) providing a non-human transgenic animal comprising a disruption in a anaphylatoxin C3a receptor gene; (b) administering an agent to the non-human transgenic animal; and (c) determining whether the function of the disrupted anaphylatoxin C3a receptor gene in the non-human transgenic animal is modulated.
- 13. A method of identifying an agent that modulates the expression of anaphylatoxin C3a receptor, the method comprising:
(a) providing a cell comprising a disruption in a anaphylatoxin C3a receptor gene; (b) contacting the cell with an agent; and (c) determining whether expression of the anaphylatoxin C3a receptor is modulated.
- 14. A method of identifying an agent that modulates the function of a anaphylatoxin C3a receptor gene, the method comprising:
(a) providing a cell comprising a disruption in a anaphylatoxin C3a receptor gene; (b) contacting the cell with an agent; and (c) determining whether the function of the anaphylatoxin C3a receptor gene is modulated.
- 15. The method of claim 13 or claim 14, wherein the cell is derived from the non-human transgenic animal of claim 8.
- 16. An agent identified by the method of claim 11, claim 12, claim 13, or claim 14.
- 17. A transgenic mouse comprising a disruption in an anaphylatoxin C3a receptor gene, wherein the transgenic mouse exhibits an abnormality of the thymus.
- 18. The transgenic mouse of claim 17, wherein the thymus abnormality is reduced weight of the thymus relative to a wild-type mouse.
- 19. The transgenic mouse of claim 17, wherein the thymus abnormality is reduced size of the thymus relative to a wild-type mouse.
- 20. The transgenic mouse of claim 17, wherein the thymus abnormality is a reduced thymus to body weight ratio relative to a wild-type mouse.
- 21. A transgenic mouse comprising a disruption in an anaphylatoxin C3a receptor gene, wherein the transgenic mouse exhibits an increased susceptibility to seizure.
- 22. The transgenic mouse of claim 21, wherein the mouse exhibits seizure-like responses at a lower dose of Metrazol relative to a wild-type mouse.
- 23. A transgenic mouse comprising a disruption in an anaphylatoxin C3a receptor gene, wherein the transgenic mouse exhibits a stimulus processing deficit relative to a wild-type mouse.
- 24. The transgenic mouse of claim 23, wherein the stimulus processing deficit is similar to that observed in schizophrenia.
- 25. The transgenic mouse of claim 23, wherein the mouse exhibits decreased prepulse inhibition relative to a wild-type mouse.
- 26. A method of producing a transgenic mouse comprising a disruption in a anaphylatoxin C3a receptor gene, wherein the transgenic mouse exhibits at least one of the following phenotypes: an abnormality of the thymus, an increased susceptibility to seizure, or a stimulus processing deficit, the method comprising:
(a) introducing a anaphylatoxin C3a receptor gene targeting construct into a cell; (b) introducing the cell into a blastocyst; (c) implanting the resulting blastocyst into a pseudopregnant mouse, wherein said pseudopregnant mouse gives birth to a chimeric mouse; and (d) breeding the chimeric mouse to produce the transgenic mouse comprising a disruption in an anaphylatoxin C3a receptor gene.
- 27. A cell derived from the transgenic mouse of claim 17 or claim 26.
- 28. A method of identifying an agent that ameliorates a phenotype associated with a disruption in a anaphylatoxin C3a receptor gene, the method comprising:
(a) administering an agent to a transgenic mouse comprising a disruption in a anaphylatoxin C3a receptor gene; and (b) determining whether the agent ameliorates at least one of the following phenotypes: an abnormality of the thymus, an increased susceptibility to seizure, or a stimulus processing deficit.
- 29. A method of identifying an agent that modulates anaphylatoxin C3a receptor expression, the method comprising:
(a) administering an agent to the transgenic mouse comprising a disruption in a anaphylatoxin C3a receptor gene; and (b) determining whether the agent modulates anaphylatoxin C3a receptor expression in the transgenic mouse, wherein the agent has an effect on at least one of the following behaviors: susceptibility to seizure and stimulus processing.
- 30. A method of identifying an agent that modulates a behavior associated with a disruption in a anaphylatoxin C3a receptor gene, the method comprising:
(a) administering an agent to a transgenic mouse comprising a disruption in a anaphylatoxin C3a receptor gene; and (b) determining whether the agent modulates at least one of the following behaviors: susceptibility to seizure and stimulus processing.
- 31. A method of identifying an agent that modulates anaphylatoxin C3a receptor gene function, the method comprising:
(a) providing a cell comprising a disruption in a anaphylatoxin C3a receptor gene; (b) contacting the cell with an agent; and (c) determining whether the agent modulates anaphylatoxin C3a receptor gene function, wherein the agent modulates a phenotype associated with a disruption in an anaphylatoxin C3a receptor gene.
- 32. The method of claim 31, wherein the phenotype comprises at least one of the following an abnormality of the thymus, an increased susceptibility to seizure, and a stimulus processing deficit.
- 33. An agent identified by the method of claim 28, claim 29, claim 30, or claim 31.
RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Application No. 60/215,467, filed Jun. 29, 2000; and U.S. Provisional Application No. 60/244,083, filed Oct. 26, 2000, the entire contents of which are incorporated herein by reference.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60215467 |
Jun 2000 |
US |
|
60244083 |
Oct 2000 |
US |