TetO-p16 transgenic mice
View Patent ↗Mice comprising a human p16 transgene operably linked to an inducible promoter and capable of controlled expression of p16 are provided. Also provided are cells, tissues, and organs obtainable from such mice, and methods for producing p16 transgenic mice.
1. A transgenic mouse, comprising a p16(Ink4a) transgene comprising an inducible promoter operably linked to a p16(Ink4a) gene consisting of the nucleic acid sequence of SEQ ID NO:14.
2. The transgenic mouse of claim 1 , wherein the inducible promoter is activated by the reverse tetracycline-controlled transactivator.
3. The transgenic mouse of claim 1 , wherein the transgene is stably integrated into a chromosome.
4. The transgenic mouse of claim 1 , wherein following induction, the p16(Ink4a) transgene is expressed in the skin of the mouse.
5. The transgenic mouse of claim 1 , wherein following induction, the p16(Ink4a) transgene is expressed in a gastrointestinal tissue of the mouse.
6. The transgenic mouse of claim 5 , wherein the gastrointestinal tissue is the tongue, esophagus, stomach, small intestine, or large intestine of the mouse.
7. A cell isolated from the transgenic mouse of claim 1 , wherein the cell comprises the transgene.
8. A tissue isolated from the transgenic mouse of claim 1 , wherein at least one cell in the tissue comprises the transgene.
9. An organ isolated from the transgenic mouse of claim 1 , wherein at least one cell in the organ comprises the transgene.
10. A method for producing the transgenic mouse of claim 1 , comprising introducing a nucleic acid sequence comprising an inducible promoter operably linked to a p16(Ink4a) gene consisting of the nucleic acid sequence of SEQ ID NO:14 into a mouse egg, embryo, or embryonic stem cell, and transferring the mouse egg, embryo, or embryonic stem cell having the introduced nucleic acid sequence into a female mouse.
11. The method of claim 10 , further comprising breeding the female mouse and selecting offspring having the nucleic acid sequence.
12. A method for producing the transgenic mouse of claim 1 , comprising introducing a p16(Ink4a) transgene comprising an inducible promoter operably linked to a p16(Ink4a) gene consisting of the nucleic acid sequence of SEQ ID NO:14 into a mouse egg, embryo, or embryonic stem cell; transferring the mouse egg, embryo, or embryonic stem cell having the introduced p16(Ink4a) transgene into a female mouse, breeding the female mouse with a male mouse comprising a reverse tetracycline transactivator transgene; and selecting offspring having the p16(Ink4a) transgene and the reverse tetracycline transactivator transgene.
13. The method of claim 12 , wherein the inducible promoter is operably linked to an operon capable of activation by the reverse tetracycline transactivator.
14. The method of claim 13 , wherein the operon is a single operon or a multimeric operon.
15. A mouse produced by the method of claim 10 .
16. A mouse produced by the method of claim 12 .
17. A method for inducing p16 expression in the transgenic mouse of claim 1 , comprising administered to the mouse an agent capable of activating the inducible promoter.
18. The method of claim 17 , wherein the inducible promoter is activated by the reverse tetracycline-controlled transactivator.
19. The method of claim 17 , wherein the agent comprises tetracycline or a tetracycline analog.
20. The method of claim 19 , wherein the analog comprises doxycycline.
21. The method of claim 17 , wherein the agent is selectively administered to a tissue of interest.
22. A method for producing the transgenic mouse of claim 1 , comprising breeding a mouse comprising a p16(Ink4a) transgene comprising an inducible promoter operably linked to a p16(Ink4a) gene consisting of the nucleic acid sequence of SEQ ID NO:14 with a mouse comprising a reverse tetracycline transactivator transgene, and selecting offspring having the p16(Ink4a) transgene and the reverse tetracycline transactivator transgene.
23. A mouse produced by the method of claim 22 .