Transgenic animals capable of being induced to delete senescent cells

Abstract

This document relates to methods and materials involved in the removal of senescent cells within a mammal. For example, transgenic non-human animals that can be induced to delete senescent cells are provided.

What is claimed is: 
     
         1 . A transgenic mouse, the nucleated cells of which contain a transgene, said transgene containing a promoter sequence operably linked to a nucleic acid sequence encoding a polypeptide having the ability to kill a cell or facilitate the killing of a cell when said transgenic mouse is administered a compound, wherein senescent cells of said transgenic mouse express said polypeptide, and wherein said senescent cells of said transgenic mouse are killed when said compound is administered to said transgenic mouse. 
     
     
         2 . The transgenic mouse of  claim 1 , wherein less than 10 percent of non-senescent cells of said transgenic mouse are killed when said compound is administered to said transgenic mouse. 
     
     
         3 . The transgenic mouse of  claim 1 , wherein said promoter sequence is a p16 Ink4a  promoter sequence. 
     
     
         4 . The transgenic mouse of  claim 1 , wherein said polypeptide comprises a caspase 8 polypeptide sequence. 
     
     
         5 . The transgenic mouse of  claim 1 , wherein said polypeptide comprises a FKBP polypeptide sequence. 
     
     
         6 . The transgenic mouse of  claim 1 , wherein said polypeptide is a FKBP-caspase 8 fusion polypeptide. 
     
     
         7 . The transgenic mouse of  claim 1 , wherein said compound is AP20187. 
     
     
         8 . The transgenic mouse of  claim 1 , wherein the genetic background of said transgenic mouse is a BubR1 H/H  genetic background. 
     
     
         9 . The transgenic mouse of  claim 1 , wherein said transgene comprises nucleic acid encoding a marker polypeptide. 
     
     
         10 . The transgenic mouse of  claim 9 , wherein said marker polypeptide is a GFP polypeptide.