Neurophilosophy

DELETION of a single gene switches the sexual orientation of female mice, causing them to engage in sexual behaviour that is typical of males. Korean researchers found that deleting the appropriately named FucM gene, which encodes an enzyme called fucose mutarotase, causes masculinization of the mouse brain, so that female mice lacking the gene avoid the advances of males and try to mate with other females instead. The findings probably have little relavence to human sexual orientation, however.

FucM is one of a family of enzymes involved in rearranging the atoms in small sugar molecules called monosaccharrides. In 2007, Chankyu Park of the Korea Advanced Institute of Science and Technology and his colleagues reported that these rearrangements facilitate the incorporation of the monosaccharide fucose into cellular proteins. This process is one of numerous chemical modifications that are well known to regulate the function of proteins, but the biological significance of FucM function in mammals was until now unclear.

Park and his colleagues therefore created genetically engineered (“knock-out”) mice lacking the FucM gene. Apart from a slight reduction in body weight, the mice seemed perfectly healthy and were no different in appearance from their normal littermates. But the researchers noticed something unusual when they put the mutant females into mating cages with normal, sexually vigorous males. Typically, the stud will approach a female, touch her body and then sniff her anal-genital region. If the female is receptive, she will invite the male to mount her, by arching her back and raising her hind quarters. But the mutant females actively avoided the advances of the males, suggesting that deletion of the FucM gene had somehow interefered with their sexual and reproductive behaviour.

In mice, sexual behaviour is mediated largely by pheromones secreted in the urine. These chemicals carry sexual signals – they enable the animals to recognize, and motivate them to approach, members of the opposite sex. Normally, females prefer the smell of male urine and vice versa, but females lacking the FucM gene were found to prefer the urine of other females to that of males, spending more time sniffing it when simultaneously presented with both. Their sexual behaviour was similar to that of males, too: they not only rejected the advances of males, but also attempted to mount and mate with other females. Nevertheless, they remained fertile – most became pregnant when forced to mate with a sexually experienced male, and the way they subsequently behaved towards their offspring was no different from normal females.  

When the researchers examined the brains of the mutant females, they observed a reduction in the number of dopamine-producing cells in the anteroventral periventricular nucleus (AVPv), a part of the hypothalamus which regulates the release of hormones required for ovulation. The AVPv is known to differ in size between males and females – it is between two to four times larger in females, and contains more cells. It is smaller in females missing the FucM gene, and thus closely resembles that of normal males. The researchers therefore hypothesized that deleting the gene causes changes in brain development that masculinize the brains of the females. 

They also speculated that the observed changes occur because deleting the FucM gene perturbs the function of alpha-fetoprotein (AFP). AFP normally protects the female mouse brain from masculinization, by binding to and sequestering the hormone oestrogen during development, and its function is thought to be regulated by the addition and removal of fucose molecules. To test this prediction, the researchers analyzed expression levels of AFP in the mutant females, and the chemical composition of the protein circulating in their bloodstream. This revealed that AFP was present at normal levels, but that there was a significant reduction in the number of AFP molecules that had fucose attached to them. 

Other researchers have shown that the neural circuits underlying male behaviours are likely to exist in the normal female mouse brain, and the reverse is probably true. It is also likely that the embryonic human brain has the capacity to differentiate along both the male and female pathways, depending upon exposure to sex hormones during the early stages of development.

These new findings show that FucM is critical for steering the developing mouse brain towards female diffrentiation. But they probably have limited relavence to human sexuality, because although FucM probably plays the same role in humans, oestrogen does not masculinize the developing human brain. There has been much talk of a “gay gene” in recent years, but no such gene has been discovered, It is, however, only a matter of time before the genes governing human sexual orientation are found.


Park, D., et al. (2010). Male-like sexual behavior of female mouse lacking fucose mutarotase. BMC Genetics 11 (1) DOI: 10.1186/1471-2156-11-62.

Comments

  1. #1 Russell
    July 15, 2010

    What an appropriate label for that protein. Hee, hee!

  2. #2 djlactin
    July 15, 2010

    Poe! (FucM; FucU).

  3. #3 Bjørn Østman
    July 15, 2010

    How is that pronounced, now? Fuk’em?

  4. #4 Crazy Mermaid
    July 15, 2010

    I welcome the research into this topic, with one caveat: this is a slippery slope into the “broken” and “not broken” labels that society will likely bestow.

  5. #5 petrossa
    July 16, 2010

    Great solution for rat infestations if it works on rats too.

  6. #6 Brian
    July 16, 2010

    This may be more an issue of gender identity than sexual orientation. The two may not be easily distinguished in mice, though.

  7. #7 LovleAnjel
    July 19, 2010

    I wonder how this compares with female mice raised only with other females (no male exposure). They are quite happy to vigorously mount each other.

  8. #8 Simon
    July 20, 2010

    Agreed with the gender identity over sexual orientation comment. If a male mistakes a male for a female is it really an issue of sexual orientation?

  9. #9 Corbier
    July 20, 2010

    Abstract:
    “although the animals were fertile due to a rare and forced intromission by a typical male”
    and the animal welfare office accepted that ? :)

  10. #10 GroovyJ
    July 20, 2010

    Do the lesbian mice attempt to mount other lesbian mice, or only unaltered females? Is their hormone production more similar to that of a male or female mouse?

    Also, RE: gay gene, I know we learned in psych 201, back in ’99, that there was solid evidence that sexual dimorphism in the human brain was caused by threshold testosterone levels, and that studies suggested a strong correlation between suppressed testosterone levels in mothers and homosexuality in their sons.

    The study that stuck in my mind was one that showed that men were substantially more likely to be gay if their mother’s home city was bombed while they were in their second trimester. High levels of stress suppress testosterone production. As far as I know, being bombed does not correlate with any gene.

    Disection of ‘gay brains’ also showed substantial difference in the development of the sexually dimorphic nucleus, and gays were also shown to produce characteristically female hormones (such as those associated with lactation.)

    On the other hand, all of this is from memories of something that came up in a class I took more than a decade ago… Maybe it was discredited, or superceded by new research, but given the dominant ideologies of the last decade, I think it far more likely that it was simply ignored.

  11. #11 GroovyJ
    July 20, 2010

    Hmmm… Well, it turns out that all of my questions were answered by clicking on one link. I’m apparently bordering on retarded, so take everything else I said with a grain of salt.

  12. #12 dream
    July 23, 2010

    Dear Crazy Mermaid,

    ~nod, nod~ as well, nature versus nurture. Ultimately it really depends on what people think of variations… Designed – astray from purpose, or is genetic mutation (natural, as opposed to engineered) part of the many factors life hands over to individuals? I don’t know if I am stretching it if I invite you to apply the same logic with the physically and mentally challenged people.

    Dear petrossa,

    Lol, there was some genetic solution to make sterile bug of some sort I think (got to check parasitology notes on that one but regardless); as Corbier repeated, they were still fertile and

    Yes, Corbier, it happens in nature all the time. I wonder if someone would complain if the female was physically bound though—wait no, now, does anyone care about the sexual act itself or the insemination? Because that is also a common practice in food industry/breeding …

    P.S. Dear GroovyJ, what’s that link you found?

  13. #13 Jack William Atkins
    July 26, 2010

    A simple case of AMYGDALIC PRE-SEXUALITY. Very common in all humans.

  14. #14 Ania
    July 27, 2010

    I think that this finding has a lot relavence to human sexual orientation.
    A long time ago we did not believe that a woman can be interested in a woman only or a man in a man only.
    This finding can explain us a little.

  15. #15 Bradley Cooke
    July 30, 2010

    Do you have citations for your assertion that progesterone masculinizes the fetal brain? I could have sworn that testosterone was responsible, e.g., as shown by XY cases of androgen insensitivity syndrome……

  16. #16 Mo
    July 31, 2010

    Well spotted Bradley. That should have been “oestrogen does not masculinize the fetal human brain” – I’ve changed it now.

  17. #17 Eggbagel
    September 10, 2010

    I think this would be much better titled “Researchers create ‘trans-gendered’ mice by deleting a single gene.” Masculanization of the brain is what caused the “lesbian” behavior. Trans-gendered would speak more truely to the mice being female but behaving as males. A male gendering is not what influences lesbian behavior in human females.

  18. #18 aidel
    September 17, 2010

    Agree with @17, sort of. The use of the word “lesbian” in the title is problematic (but so is the use of trans-gendered), not only for it’s anthropomorphism, but also because what the study is really exploring is the masculanization of female mice, which, even though it may cause females to mount other females, does not a lesbian make. I appreciate that you pointed out (several times) that no inferences can be made regarding human sexual behavior. I think you could have said it 100 more times and that wouldn’t have been too many! Perhaps I’m old and have lost my sense of humor (although I do love the word FUCK, perhaps a little more than is appropriate for a dowdy, middle-aged mother), but I think naming the enzyme FucM was a very unfortunate mistake (and possibly even misogynist). Is their similar research conducted on the feminization of male mice? And I can’t help wonder why “forced intercourse” was employed rather than artificial insemination? Perhaps it takes more time, energy, effort and money — but I, too, find it curious that this would be acceptable to any animal research review board (although given that rape in humans is socially sanctioned, I guess it shouldn’t be a surprise). It’s almost enough to make me want to take up arms with a violent, lesbian separatist, PETA group. Almost. Not quite. Oh, FUCK ‘EM.

  19. #19 aidel
    September 18, 2010

    What is also a bit of a surprise to me is that I didn’t see anyone mention what may be a real (and significant) implication of this study: that, given the right “equipment,” males make perfectly fine nurturers of the young.

  20. #20 ajay
    October 4, 2010

    i am human whos body dont react and participate in
    gay sex in human brain

  21. #21 Saberfang321
    June 15, 2011

    Anyone know if they’re releasing these lesbian mice to petstores? haha, I’m dying to get my hands on some to make a lesbian mice farm LOL

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