With a switch of a letter in DNA ‘dark matter,’ Israeli scientists change sex of mouse

Thanks for the opportunity to nerd out in public. I think the fact that a single cell can grow and divide and change into all the complicated organs inside the body is totally amazing.

Ahh ok. That does make more logical sense. Either way this is above my pay grade so thank you for being the one who understands this stuff for us all! 😂

Depends what they are looking at and whether sex would influence the results. Experiments should always take into account the sex of the mice being used though so either stick to all males or all females, unless of course the experiment is looking at differences between the two.

May I ask a question? @Geneticsbunny when testing things on mice, do they usually test on male mice to avoid the hormone changes around female cycles? I’m talking about general scientific research. I never thought to ask when I worked in a university.

Arent sexual characteristics and sex characteristics the same thing at a biological level?

It would need a different gene or set of genes switching off to change an xy mouse to develop female sex characteristics. E.g. the sry gene.

As others have said they have basically created a new DSD.

I'm unclear reading the Times of Israel article in what context she made those remarks. Was she asked by journalists specifically about gender and did she have to say something without getting the TRA's heckles up? Or did she volunteer these? This is a very good piece of work, I'd be annoyed if all a journalist would ask me about it was centered around fecking gender.
Directed mutagenesis has been used for decades to study biological processes, it's bread and butter stuff for biochemists, it's great to see that non-coding DNA is getting the attention it deserves.

This is a great summary.

For those asking why they did this and what the possible applications are - this isn’t applied research like development of a treatment for a disease. As @Geneticsbunny and others have said, the aim is to get more of an understanding of how sex differentiation works. Making mice with engineered DSDs is simply a research tool to learn more about the genetics behind the developmental pathways.

No mouse will come and tell me, ‘Look, I’m a female, but I feel like I’m a male,'” she said. “Those are things that are really hard to study, but we know they are there.”

Maybe they've just not found the right kind of squeaks yet.

It is just a primary research - adding to understanding how the DNA modification by crispr works, but published with a big fuss because it vaguely touches a hot topic.

Hah, @RedToothBrush, crossposted! (I was slow to hit the button.)

They created a DSD in the mouse.

This might possibly prove a game-changer in some strands of genetics research, but it's nowhere near godlike control of a mammal's sex. Can't blame them for positioning their report within such a fashionably hot topic, though..

Basically it sounds like they've effectively created a sex chromosome developmental disorder created in the womb like a DSD but are labelling it as a breakthrough to help transpeople who transitioned later in life.

That's pretty fucked up on multiple levels.

I'm guessing that this dark matter still doesn't mean an adult female mouse can grow a penis and start producing sperm. Nor do I suspect it will mean an adult male mouse can grow ovaries and carry a baby mouse.

Nor would I suspect this to be possible with a juvenile baby mouse given when ovaries the eggs within them develop.

This story kind of created an idea of false hope. For it to be done to humans you would
A) have to break a lot of medical ethics
B) experiment on children
C) have parents of a particular strong mindset.

I also had a look at the reviewers comments (you can access the file at the bottom of the article). Scientists always want to over-emphasise the importance of their work but it's interesting to see what one of the reviewers picked up on from the original paper that got changed.

The authors originally said: "Here we show that XX mice carrying a 3 bp deletion or a 1 bp insertion within the SOX9 binding site (BS) of Enh13 present
complete female-to-male sex reversal."

And the reviewer commented: "The term “complete” may be misleading, since XX mutants exhibit ovotestis development (see Figure 2) and lack germ cells in adulthood." which led to the change in the final paper.

But then in the press release they're back to talking about "complete sex reversal" again
https://www.eurekalert.org/news-releases/1122852

Could also be groundbreaking in switching off genes that increase cancer risk or any catastrophic genetic conditions - start with a clear yes/no result, then move on to conditions that come through most strongly via one parental line, etc, etc.

They added or removed a small number of base pairs of DNA at a specific location and the XX mice developed visually as males but they had small testes and didn't produce sperm (so were infertile).

"Here, we show that XX mice carrying a 3 bp deletion or a 1 bp insertion within the SOX9 binding site (BS) of Enh13 present with female-to-male sex reversal. Adult XX mice appear externally and internally as males, but with small testes devoid of sperm due to the lack of the Y chromosome"

Actually female is the default normally. I didnt explain that very well. Its a bit complicated because cells start as default cells which can be anything called stem cells. Then different genes are switched on and these switch on other genes which switch on other genes which turn the cells into kidney cells or testicle cells.

Basically if the gene in the paper (sox9) cant be switched on then there are more genes switched on which push the cells towards the testicle cell fate than those which would push the cells to be ovary cells.

“No mouse will come and tell me, ‘Look, I’m a female, but I feel like I’m a male,'” she said. “Those are things that are really hard to study, but we know they are there.”

I want to know how they know that some male mice feel female and vice versa. Or is this badly written up, and she's acknowledging this in humans (gender dysphoria) but making no comment on mice? If it were the case in mice, that would be one hell of an argument in favour of an innate gender. But it's kind of hard to imagine it is. I mean, can they even conceive of themselves as individuals, or conceptualise sex difference, in the ways I'd assume would be necessary for this?!

That’s interesting the male is default. As it’s XY you would think the Y is then important male part and the X the default. Strange

I dont think making people infertile is an ethical way of stopping genetic disease! Pretty sure the nazis tried that already and it didnt end well for anyone.
Plus gene editing human embryos and allowing them to grow is illegal worldwide because we dont have a good enough understanding of the techniques and consequenses yet. .

Oh Frankenstein much.

I suppose one reason for doing it could be, apart from to find out if they can, is because there are conditions that can get passed on from mother to child, and maybe this could lead to a way that could be prevented in future. 🤷‍♀️