Rabbit vs. Mouse Antibodies: What's the Difference?
Have you ever opened your lab’s freezer and seen two almost identical vials for the same target and same epitope with different serial numbers? You might at first think that maybe someone at the antibody company messed up the label or that your PI is just hemorrhaging money on duplicates until you look a little bit closer and realize that one was produced in rabbit and one was produced in mouse. Oops, time to go back and re-read that methods section to make sure you pick the right one…
Rabbits and mice are both very highly used research organisms. We immunize both to this day as we manufacture new antibodies.
Why would you choose one over the other, if both antibodies will recognize the same target and same epitope?
Before the invention of rabbit monoclonal antibodies, researchers relied primarily on rabbit antisera or mouse monoclonal antibodies for the development of antibodies. The issue with rabbit antisera (or as we would call it today, polyclonal rabbit antibodies) is the crudeness of epitope recognition and the tie that such a reagent has to the lifespan of a specific animal. Mouse monoclonals, however, are based on a single epitope and are immortalized as hybridomas. Even better, mouse husbandry is much less resource-intensive than farming rabbits is. So why was the development of a rabbit monoclonal antibody such a breakthrough?
If we were to pit mice and rabbits head-to-head, rabbit antibody production effortlessly wins. Antibody diversification in rabbits occurs via two processes. In mice, only somatic hypermutation occurs to diversify antibody structure. Rabbits, however, undergo gene conversion as well, which results in a larger array of antibody structures than is accessible to mice alone. Moreover, rabbit antibodies are typically 10-100 times more sensitive than mouse antibodies, which is partially due to the genetic diversity of the antibodies, but also can be attributed to extra structural features in the binding loops of rabbit antibodies. It also helps that rabbits are less evolutionarily related to humans, which makes the immunization process easier. Mice, which are more closely related to humans, can at times struggle with eliciting an immune response to a human immunogen.
This doesn’t mean that mice are losers. Even though rabbit monoclonals are a gold standard for specificity, mouse monoclonals still offer a lot of value to life sciences researchers. Foremost, mouse monoclonals offer a better price point for researchers who don’t necessarily need extreme specificity. If you’re just running a quick western blot, a mouse monoclonal for the same target as a rabbit monoclonal should do just fine if you are constrained by availability or cost. Additionally, accessing both mouse and rabbit monoclonals offers the potential for multiplexing, so having epitope redundancy across multiple host species works in favor of researchers with complicated experiments.
Beyond mice and rabbits, there are many other host species that researchers have developed antibodies in, but these hosts are quite rare. At HUABIO, a majority of our antibodies were produced in mouse or rabbit, but we have a select few additional host species. Primarily, our secondaries that bind to mouse/rabbit IgG must be produced in a different species to avoid cross-reactivity. The majority of ours are produced in goat and some alpaca (though conventional alpaca antibodies are rare, since alphas produce heavy-chain-only antibodies, from which nanobodies are derived!).
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