I am injecting a plasmid into FVB mice using the hydrodynamic tail vein protocol laid out in many papers including this one on the Jove website:

https://www.jove.com/video/51481/transient-expression-of-proteins-by-hydrodynamic-gene-delivery-in-mice

We have followed every step very carefully, I am quite skilled at tail vein injections and can do them without anesthesia so that is not a problem. However, unless we drastically decrease the volume the mice die almost immediately after injection. I have yet to have a mouse survive more than 1ml of saline injected over the course of 5 seconds. We are using a heating pad to try to warm them up after the injection, and do not anesthetize them during the injection. Every protocol I have read says they should be able to withstand 10% of their body weight in mls, but I can't imagine getting anywhere near that volume.

Any advice would be helpful, I can't figure out what is going wrong.

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