This feels like the most sensitive post I’ve ever made. If I could do something better I’m happy to consider it.
There are some fascinating mice I’ve wanted to post about. Mice in which the TrpC2 gene has been deleted (TrpC2-/-, +/- is heterozygous). First I need to do a little set up.
Humans and Trp2C.
It’s about most of the rest of vertebrates vs. “old world” primates (parvorder Catarrhini). The old world primates include gibbons and great apes like us, and they lack a vomeronasal organ and accessory olfactory system as I mentioned in the other post some posts ago. So no pheromone system and other things that this system did for us. But I believe the evolutionary event of TrpC2 wreckage in human ancestors had a significant effect on us for better and worse.
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And in that other post I pointed out how the accessory olfactory system and pheromones themselves are devoted to a range of behaviors beyond mating. Going into predator and prey or food, and a large range of information about your own kind like age, sex, relatedness, health status and more. Whole information channels now missing, but with still existing brain hardware downstream from that olfactory system.
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Trp2C is a cation channel protein, “transient receptor potential 2C” (Ca2+, Na+). It is located in the same part of vomeronasal sensory neurons as the vomeronasal olfactory receptors and is part of the signalling system that activates the neuron during signal transduction. In humans this is a pseudogene, it contains a bunch of extra termination codons that severely truncate the protein making it non-functional. It’s an obvious experiment to delete the gene in a model organism like the mouse and see what happens and so some scientists did that.
Before I introduce the mice I want to emphasize that humans have a whole evolutionary history that includes other accessory olfactory pseudogenes, and other changes I think of as “things sandwiched between stimulus and impulse”. These mice are creatures we made in a lab without the 25-40 million years of extra evolution since we lost our Trp2C. There will be implications for good and bad things.
The TrpC2 deletion mice.
These mice lose their social aggression for one thing. They’ll defend themselves if attacked but don’t do any attacking themselves. Males stop fightng intruder males. Females stop fighting intruder males during lactation. Males stop being aggressive towards juveniles. They don’t seem to form dominance hierarchies (as measured by urine marking patterns, the dominant mouse gets to go everywhere, everyone else goes in a corner). TRICK or TRP? What Trpc2−/− mice tell us about vomeronasal organ mediated innate behaviors. Yu 2015
Females don’t engage in nest building as often and don’t nurse as often, but offspring numbers are the same and they have similar body weight so maybe they nurse more effectively. Trpc2 gene impacts on maternal aggression, accessory olfactory bulb anatomy and brain activity. Hasen 2009.
Males care for offspring more, though not to the level of females. Vomeronasal signal deficiency enhances parental behavior in socially isolated male mice. Orikasa 2017
Examples of lost behaviors? TrpC2-/- mice can’t detect sick mice anymore for one thing. Sensing and avoiding sick conspecifics requires Gαi2+ vomeronasal neurons. Weiss 2023.
And then there’s sexual behavior.
This paper describes the big ideas. The De-Scent of Sexuality: Did Loss of a Pheromone Signaling Protein Permit the Evolution of Same-Sex Sexual Behavior in Primates? Pfau 2021.
The first thing to mention is that all of these behaviors were already present at low levels in wild type mice (as they are in primates with an accessory olfactory system). These studies describe increases in rates of various behaviors. The same goes for the previous behavior but I wanted to make the point here. There’s no “gay gene” here since the same sex behavior was already there. It’s more like existing sex specific behaviors increased rates and spread out to both sides once they lost olfactory control.
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Both male and female TrpC2-/- mice will mount males or females during intruder experiments instead of fighting. At other times too but this was the really noteworthy experiment since fighting an intruder is the typical response of the non-mutant mice.
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It gets more detailed. Female TrpC2-/- mice also scent mark like males, vocalize like males, engage in exploratory anogenital sniffing like males (which males usually do during courtship), and they do this thing where they lift up the other mouse’s rump with their nose like males. The behavior between the male and female TrpC2-/- mice get described differently in the literature early on with the male mice merely engaging in same sex behavior but the females show “male type sexual behaviors”. A functional circuit underlying male sexual behaviour in the female mouse brain. Kimchi 2007.
The tough subject, the bad one.
Trigger warning: implications about child sexual abuse.
A final sexual characteristic of the TrpC2-/- mice is they no longer respond to a protein secreted from juveniles that suppresses such behavior (ESP22). These mice were used in the following paper to study this phenomenon. A juvenile mouse pheromone inhibits sexual behaviour through the vomeronasal system. Ferrero 2013. These mice express sexual behavior towards juveniles at higher rates than wild type mice. This is the tough subject because it’s explanatory of problems we’re dealing with as a society, just as the other observations are explanatory of things that aren’t problems because of consent and similar developmental stages between individuals.
This is explanatory for why should such things even exist. It’s in the same box as murder, it’s possible for some of us, but implicitly harmful. A violation of power. I’m of the opinion that in order to control ourselves as a group it helps to understand ourselves as a group and I believe these mice help there.