Claims
- 1. A targeting construct comprising:
(a) a first polynucleotide sequence homologous to a target gene, wherein the target gene a lymphoid-specific GPCR gene; (c) a second polynucleotide sequence homologous to the target gene; and (d) 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 for a lymphoid-specific GPCR gene, the method comprising:
(a) obtaining a first polynucleotide sequence homologous to a lymphoid-specific GPCR gene; (b) obtaining a second polynucleotide sequence homologous to a lymphoid-specific GPCR gene; (c) providing a vector comprising a selectable marker; and (d) inserting the first and second sequences into the vector, to produce the targeting construct.
- 4. A method of producing a targeting construct for a lymphoid-specific GPCR gene, the method comprising:
(a) providing a polynucleotide sequence homologous to a lymphoid-specific GPCR gene; (b) generating two different fragments of the polynucleotide sequence; (c) providing a vector having a gene encoding a selectable marker; and (d) inserting the two different fragments into the vector to form the targeting construct.
- 5. A cell comprising a disruption in a lymphoid-specific GPCR 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 a lymphoid-specific GPCR 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 lymphoid-specific GPCR 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 lymphoid-specific GPCR, the method comprising:
(a) providing a non-human transgenic animal comprising a disruption in a lymphoid-specific GPCR gene; (b) administering an agent to the non-human transgenic animal; and (c) determining whether the expression of lymphoid-specific GPCR in the non-human transgenic animal is modulated.
- 12. A method of identifying an agent that modulates the function of a lymnphoid-specific GPCR gene, the method comprising:
(a) providing a non-human transgenic animal comprising a disruption in a lymphoid-specific GPCR gene; (b) administering an agent to the non-human transgenic animal; and (c) determining whether the function of the disrupted lymphoid-specific GPCR gene in the non-human transgenic animal is modulated.
- 13. A method of identifying an agent that modulates the expression of lymphoid-specific GPCR, the method comprising:
(a) providing a cell comprising a disruption in a lymphoid-specific GPCR gene; (b) contacting the cell with an agent; and (c) determining whether expression of the lymphoid-specific GPCR is modulated.
- 14. A method of identifying an agent that modulates the function of a lymphoid-specific GPCR gene, the method comprising:
(a) providing a cell comprising a disruption in a lymphoid-specific GPCR gene; (b) contacting the cell with an agent; and (c) determining whether the function of the lymphoid-specific GPCR 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 a lymphoid-specific GPCR gene, wherein the transgenic mouse exhibits cellular infiltration.
- 18. The transgenic mouse of claim 17, wherein the cellular infiltration is comprised of lymphocytes.
- 19. The transgenic mouse of claim 18, wherein the cellular infiltration occurs in any one of the following organs: lung, pancreas, stomach or liver.
- 20. The transgenic mouse of claim 17, wherein the transgenic mouse is heterozygous for a disruption in a lymphoid-specific GPCR gene.
- 21. The transgenic mouse of claim 17, wherein the transgenic mouse is homozygous for a disruption in a lymphoid-specific GPCR gene.
- 22. A method of producing a transgenic mouse comprising a disruption in a lymphoid-specific GPCR gene, wherein the transgenic mouse exhibits cellular infiltration, the method comprising:
(a) introducing a lymphoid-specific GPCR 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 a lymphoid-specific GPCR gene.
- 23. A transgenic mouse comprising a disruption in a lymphoid-specific GPCR gene, wherein the transgenic mouse exhibits at least one of the following phenotypes: peribronchiolar cellular infiltrates in the lungs; periductular cellular infiltrates in the pancreas; cellular infiltrates in the deep mucosa, submucosa, or muscularis of the stomach; or cellular infiltrates in the portal triads of the liver.
- 24. A cell derived from the transgenic mouse of claim 17, claim 22 or claim 23, wherein the cell comprises a disruption in a lymphoid-specific GPCR gene.
- 25. A method of identifying an agent that ameliorates cellular infiltration, the method comprising:
(a) administering the agent to the transgenic mouse comprising a disruption in a lymphoid-specific GPCR gene; and (b) determining whether the agent ameliorates cellular infiltration in the transgenic mouse.
- 26. The method of claim 25, wherein the cellular infiltration is comprised of lymphocytes.
- 27. The method of claim 26, wherein the cellular infiltration occurs in any one of the following organs: lung, pancreas, stomach or liver.
- 28. A method of identifying an agent which modulates lymphoid-specific GPCR expression, the method comprising:
(a) administering an agent to the transgenic mouse comprising a disruption in a lymphoid-specific GPCR gene; and (b) determining whether the agent modulates lymphoid-specific GPCR expression in the transgenic mouse, wherein the agent modulates a phenotype associated with a disruption in a lymphoid-specific GPCR gene.
- 29. The method of claim 28, wherein the phenotype comprises cellular infiltration in any one of the following organs: lung, pancreas, stomach or liver.
- 30. The method of claim 29, wherein the cellular infiltration is comprised of lymphocytes.
- 31. A method of identifying an agent which modulates lymphoid-specific GPCR expression, the method comprising:
(a) providing a cell comprising a disruption in a lymphoid-specific GPCR gene; (b) contacting the cell with the agent; and (c) determining whether the agent modulates lymphoid-specific GPCR gene expression, wherein the agent modulates a phenotype associated with a disruption in a lymphoid-specific GPCR gene.
- 32. The method of claim 31, wherein the phenotype comprises cellular infiltration in any one of the following organs: lung, pancreas, stomach or liver.
- 33. The method of claim 32, wherein the cellular infiltration is comprised of lymphocytes.
- 34. A method of identifying an agent which modulates lymphoid-specific GPCR gene function, the method comprising:
(a) providing a cell comprising disruption in a lymphoid-specific GPCR gene; (b) contacting the cell with an agent; and (c) determining whether the agent modulates lymphoid-specific GPCR gene function, wherein the agent modulates a phenotype associated with a disruption in a lymphoid-specific GPCR gene.
- 35. The method of claim 34, wherein the phenotype comprises cellular infiltration in any one of the following organs: lung, pancreas, stomach or liver.
- 36. A method of identifying an agent which modulates a phenotype associated with a disruption in a lymphoid-specific GPCR gene, the method comprising:
(a) administering an agent to a transgenic mouse comprising a disruption in a lymphoid-specific GPCR gene; and (b) determining whether the agent modulates the phenotype.
- 37. The method of claim 36, wherein the phenotype comprises cellular infiltration in any one of the following organs: lung, pancreas, stomach or liver.
- 38. An agent identified by the method of claim 25, claim 28, claim 31, claim 34 or claim 36.
RELATED APPLICATIONS
[0001] This application is a continuation-in-part to U.S. application Ser. No. 60/190,348, filed Mar. 16, 2000 and U.S. application Ser. No. 60/221,485, filed Sep. 27, 2000.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60191128 |
Mar 2000 |
US |
|
60221485 |
Jul 2000 |
US |