Yes it is possible to do in vivo knockouts. We've done MDA-MB-231 xenografts commercially (http://altogenlabs.com/xenograft-models/breast-cancer-xenograft/mda-mb-231-xenograft-model/) and we've also made in vivo transfection reagents (https://altogen.com/product/in-vivo-transfection-kits-peg-liposome-nanoparticle-polymer-lipid-tissue-targeted/) for, trivially, the in vivo based knockout of given genes. You should be careful though - inducible knockouts are only transient, and you'll either have to use systemic administration or have a clear way to deal with the transient nature of the knockout in your research.

I have never personally done this but, it seems it should be possible. Off the top of my head:

I would consider first transfecting the cell line with an inducible siRNA (or shRNA) for the gene of interest. To this end, I would consider rather a viral tranfection system that would incorporate into the genome rather than a plasmid as you may lose the plasmid over time. Also, there exist a number of commercially available/well described transfection systems that have an inducible promoter region, typically induced by a drug such as doxycycline, which could later be delivered via the animals' drinking water, food, gavage, or injection. In the case of a genome incorporating transfection system I would double check to make sure the drug that induces my siRNA gene can penetrate the nucleus.

Of course you would have a fair number of validation steps before you actually make the graft in animals and then you would have further validation steps along with expanding the number of required controls (healthy animals, healthy animals + inducing drug, normal cells, normal cells + inducing drug, empty vector, empty vector + inducing drug, modified vector, modified vector + inducing drug,etc.).

There is a paper about a rat model that uses a similar idea, but not in a xenograft, rather the animal itself. The group bred rats to express an engineered tetracycline inducible shRNA gene that would knockdown insulin receptor expression to induce diabetes. Different from what you want to do but similar.

Title: Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown

Available: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005124

As I said, I have never personally tried this but I hope I may have sparked an idea for you. I have used shRNA in vitro and viral vector transfection and xenografts all seperately, I have just never tried combining them. I also don't personally know of something like this having been done, but perhaps someone else with more expertise or experience than me can provide additional insight. I wish you luck because if it works this would be a very useful tool.

-Zack

Yes it is possible to do in vivo knockouts. We've done MDA-MB-231 xenografts commercially (http://altogenlabs.com/xenograft-models/breast-cancer-xenograft/mda-mb-231-xenograft-model/) and we've also made in vivo transfection reagents (https://altogen.com/product/in-vivo-transfection-kits-peg-liposome-nanoparticle-polymer-lipid-tissue-targeted/) for, trivially, the in vivo based knockout of given genes. You should be careful though - inducible knockouts are only transient, and you'll either have to use systemic administration or have a clear way to deal with the transient nature of the knockout in your research.