Erasmus University Medical Center Rotterdam

Buck Institute for Research on Aging

James Mitchell

Judith Campisi

Remi-Martin Laberge

Marco Demaria

Francis Rodier

Jan H J Hoeijmakers

Wendy Toussaint

This invention provides a transgenic mouse with a p16promoter sequence that controls expression of a protein such that it is expressed preferentially in senescent cells. The protein either directly induces apoptosis, or converts a prodrug to a cytotoxic compound. In addition, the mouse is injected with syngeneic tumor cells, or has second transgene that causes tumors to form. Removing senescent cells from the mouse may result in the formation of fewer tumors.

Transgenic mouse for determining the role of senescent cells in cancer

This invention provides a transgenic mouse for studying the role of senescent cells on an age-related disorder or an age-sensitive trait. The transgene contains a p16 promoter sequence that controls expression of an enzyme so as to cause the enzyme to be expressed in senescent cells in the mouse. The enzyme converts a prodrug to a cytotoxic agent, so that treating the mouse with the prodrug results in the prodrug selectively killing the senescent cells. As a result, progression of an age-related disorder or an age-sensitive trait is delayed. Included is the 3MR mouse model, which also expresses bioluminescent and fluorescent markers under control of the p16 promoter so that senescent cells in the mice can be visualized.

Transgenic mouse having a transgene that converts a prodrug into a cytotoxic compound in senescent cells

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Boston, MA, United States of America

James Mitchell