Researchers Create "Mighty Mouse" With Gene Tweak 112
cylonlover writes "He can't fly just yet, but a team of scientists have made a big step towards creating a real-life Mighty Mouse. By tweaking a gene that normally inhibits muscle growth the researchers created a batch of super-strong mice and worms. The scientists acted on a genome regulator — known as NCOR1 — and were able to change the activity of certain genes. In simpler English, the scientists shut off the thyroid hormone that keeps most mammals from turning into the Incredible Hulk. The result was a strain of mice with muscles that were twice as strong as normal."
Give to 1 area, ur taking from another (Score:1, Insightful)
I figure it this way: You give these mice that growth of musculature, something's going to take a beating (probably lifespan), because the body's designed to only grow so much in that area, there must be a reason, a LONG TERM REASON, why.
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Once we're there, then we can work on gene therapy for the tendons and bones.
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Sometimes the compromise is nothing more than food availability. Perhaps 'mighty mouse' would be less able to weather a famine, but that's unlikely in the lab setting.
Re:Give to 1 area, ur taking from another (Score:4, Insightful)
I reject the notion that mice were "designed" or that a mouses body is the way it is due to any reasoning.
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One meaning of the word reason is "explanation". We can explain why many genetic traits have been beneficial and helped a species to survive and propagate. He didn't say anything about "due to reason", he said "there must be a reason".
Re:Give to 1 area, ur taking from another (Score:4, Insightful)
"reason" wasn't the problematic term, "designed" was, as in "... the body's designed to ...".
It is not designed to do anything, because it isn't designed in the first place.
However, even the reason part is crap. "There must be a reason, a LONG TERM REASON" is just plain wrong.
Evolution makes no claims of optimal outcomes in the first place.
Maybe said mutation just never happened in the wild? Maybe the disadvantages it also produced are no longer disadvantages due to environmental changes or other genome changes? Maybe it doesn't actually give an advantage to survival or reproduction? Maybe is requires more energy input which is bad in the short term? Maybe there's one of a million other short term disadvantages that don't apply in a lab setting.
Assuming it must be bad is the antithesis of evolution - a theory in which the core concept is that such a change might be beneficial.
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Yep, though it's easy to let words like design and creature slip into this kind of thing even if you're not religious. What you're saying is repeated so often that I just would assume he already knows it, thougn I may be wrong of course. It's okay to point out common mistakes, but it's just as bad if you repeat the "truth" without thinking. It's groupthink ast its worst.
Reason was a valid word in context, taken to mean "explanation". Not an explanation by some anthropomorphic incarnation of evolution, but b
Aren't we touchy... (Score:2)
Most beings are sufficiently well organized that is very much as if they were designed. Although I disapprove of needless capitalization, to use the ideologically correct version of his statement might be something like: ... because the body evolved to only grow so much in that area, there is likely a specific disadvantage to making it otherwise....
It is more than just correct, it is technically correct, thus should please the petty pedants.
Personally, I prefer the abstract application of 'design' and 're
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"likely" and "must be" are very different.
"a specific disadvantage" and "a LONG TERM REASON" are very different.
Your words are general and hedged. The original claims are specific and set in stone.
I agree, here is likely some reason animals aren't supercharged like this already - most likely in my mind would be energy requirements (weaker but needing less food leads to better survival than stronger but needing more food) but I know nothing about the specifics or if there are even additional energy needs.
Survival... (Score:1)
A mouse needs to be able to run at full speed under a closed door. Otherwise it may be hacked to death by the bloke chasing it with a carving knife (or eaten by the kitty)
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Oh, there are probably selection reasons, but this doesn't prevent human applications, because the recent 1M years of evolution and selection pressure may have no relevancy at all to the human context. Consider human age limits? Why is the human not evolved to live longer? The answer is probably "there was no particular evolutionary need/utility for that". I.e., once you have birthed children and raised them to adults, you have no further "use" to your selfish gene. Defeating that is beneficial to us, but n
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How did this get an insightful mod? Clearly flame bait. The commenter didn't put any emphasis on the word designed.
They were just pointing out, regardless of whether you believe in evolution or creationism, that there is likely some purpose served by the presence of a limiting hormone. Thus, by eliminating that trait, you can expect there might potentially be side effects. Of course it might be some evolutionary artifact that is no longer necessary in today's environment, but I wouldn't place bets on th
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Re:Give to 1 area, ur taking from another (Score:4, Funny)
You give these mice that growth of musculature, something's going to take a beating
Yeah, any unaltered mice are going to take a beating for sure.
That's a given (Score:2)
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Living a sedentary life style leads to chair-butt, it's a fact, and proven.
Just look around the cubicle farm. =)
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Not for everyone. I have to over eat a huge amount to put on weight, like 3.5k or 4k calories a day. And even then I'll only gain it really slowly and very evenly. I build muscle in the blink of an eye and fat just melts off naturally if I eat a normal amount of food without any effort. My ex is pencil thin no matter what she eats, literally doesn't gain mass. And she's uber unfit, contains no muscle.
So no, sedentary lifestyles do not lead to chair-butt in all people. It's actually a proven fact. There's
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But by that logic, leading a sedentary lifestyle will lead to long life. Everyone is different and some people put on muscle mass way faster than others, just from their natural genetics. Being able to put muscle on easier than average is far from a sure ticket to a heart attack.
So you are saying that either hulked out mutated muscles are the healthiest way to live, or a sedentary person that never moves a muscle is the healthiest way to live?
No room in your hypothesis for a middle ground that doesn't go all the way to one enormous extreme being the best?
Re:Give to 1 area, ur taking from another (Score:4, Insightful)
Speciation is not about some 'ultimate lifeform' so much as it is about lifeforms that are best adapted to their niche and environment. Predatory birds need top eyesight to catch quick small prey on the ground. We don't need it because our prey was usually bigger, or stationary (being omnivores). By the same token mice might just not have needed more strength to survive. Furthermore, and more importantly, if environmental pressures were such that only stronger mice were surviving, you could damn near bet money that these sorts of genetic changes would occur naturally. In a model of punctuated equilibrium, you'll find that changes usually occur when they have to, not simply because they are 'objectively better' in some abstract sense that doesn't significantly impact survival rate in a given environmental condition.
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There are tradeoffs
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I can tell you right now what the negative results are likely to be.
The super mice are less adept at surviving periods of starvation.
We're living in an age where some humans have conquered hunger and can eat as much as they want, when they want. Yes, much of the worlds population may not have all the food they want, but enough of us do that we have the luxury to get between a chair an computer screen and be oblivious to hunger.
The reason these genetic inhibitors have probably evolved is to stop the orga
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Yeh, if there is a process that has evolved/design(whatever your belief system is) to specifically limit muscle growth, then there is indeed likely a negative side effect to disabling limiting process. Perhaps animals without this regulator burned more calories and thus had to consume more food than was available to survive. Thus the mammals that developed that limiter were able to survive longer on less food. That's just one speculation, but the point is there should be alot of study into the side effec
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Not necessarily.
There are plenty of adaptions that make sense from a survival standpoint that don't make sense from a design standpoint. Immediately apparent, a body would limit growth in an environment where food is scarce. The increased protein required wouldn't hurt a rat in a cage fed a balanced diet, but could cost a rat in the wild its survival. Hence, despite having a more powerful body without real consequences, the mouse with this gene would be less survivable and thus the trait would be phased out
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There's a very good long-term reason: starvation.
In centuries past, there was a very good probability - almost a certainty - that you would undergo occasional, extended periods of lack. An animal that has too much unnecessary muscle mass would be less able to survive this deprivation.
Modern, industrialized humans don't have this problem, though. If anything, we suffer from too little lack. We never fast, and the genes that carry out repairs during times of fasting never get turned on.
From a health perspecti
Wait a minute. (Score:5, Insightful)
I have this sneaking suspicion that if genome 'brakes' are present in most animals, they're probably there for a reason.
I wonder what sort of long term side effects you'd be looking at with vastly increased muscle growth.
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I wonder what sort of long term side effects you'd be looking at with vastly increased muscle growth.
The kind that Hitler was looking for. Best case scenario, you get parents who try to guarantee their child is the next star quarterback. Just imagine, a world full of quarterbacks. Well, except for the poor people.
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You miss the problem. It is a gene defect for a reason. The muscles are growing, but the blood vessels don't adapt accordingly. This gives those animals (there are humans with this defect, too), a tremendously lower endurance. Definitely anti-quarterback.
Re:Wait a minute. (Score:5, Informative)
The article also notes that they have not yet identified any negative effect on the mice. In fact, they say the super mice are all around healthier.
There may be some negative aspect (beyond needing more food), but TFA makes it sound like this process does indeed produce a superior quarterback. At least it does in mice.
Re:Wait a minute. (Score:4, Interesting)
Maybe... A few posts above I added some links with a certain brand of cattle with the same or similar gene defect. In the documentation I once saw about those, this was their major problem. But of course, between a ton of cattle and a few grams of mouse there might be a difference.
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Where is the video of the musculature-enhanced bull fucking a cow to death?
Or does their junk shrink like the gym junkies?
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"beyond needing more food"
That's exactly why it doesn't happen in the nature. It's not that hard to grow additional muscle mass - bodybuilders do this all the time, for example. However, you need quite a lot of additional energy to maintain them.
In case of mouses, additional endurance and strength probably does not offset the increased energy expenditure in nature.
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I have a theory that the rash of kids that were injected with HGH to make them taller (because their parents wanted them to be more successful) in the 1980's and 1990's will start dropping dead of heart attacks in about 10-15 years because their hearts did not grow large enough to support their increased height.
I knew several rich kids who's parents got them growth shots when I was a teacher in 1990, and I suspected then that it may not be a good idea. This may be a case where the meek do inherit the earth
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Enlarged heart is not in and of itself a "problem". Pick out your favorite high endurance athlete. I guarantee you: they have an enlarged heart.
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I think I saw that movie.
Re:Wait a minute. (Score:5, Insightful)
Re:Wait a minute. (Score:5, Insightful)
The most intuitively obvious answer is that if your muscle growth can't be limited you're more likely to starve to death during famines.
However I wouldn't be surprised if unchecked muscle growth also leads to bone/tendon damage/poor muscle control/heart issues etc.
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I wouldn't be surprised if unchecked muscle growth also leads to bone/tendon damage/poor muscle control/heart issues etc.
I think that would probably be the most likely scenario, if not simply because people with these sorts of mutations IIRC tend to have shortened lifespans and various health issues. There's something to be said about how biology doesn't give a crap about how a gene got there and all, and that activating something doesn't necessarily mean there will be side effects, but we're talking about genes that affect the growth and development of the physiology of the animal here, not some gene that will have no oth
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Agreed about the potential for heart issues and/or
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I have never understood why the body evolved such that in times of a severe calorie deficit, it will burn muscle before it burns it's fat stores, by default.
As far as I understand, it takes less energy to burn muscle then it does fat. So the body is going for the process that will require the least energy expense (which could be important in a severe calorie deficit). The reason it doesn't make sense is that we might require our muscle in order to get more calories, but I don't think the lower level brain makes that kind of a distinction. It's not worried about surviving the next week, it's worried about surviving RIGHT NOW.
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True, that. Also, I would wager that in a starvation situation, it's not the fact you lack muscle which is the biggest issue, but the Ice Age, or bad droughts, or other factors beyond your control. In that case saving as much energy as possible would do more for you than saving muscle. If there's plants or roots to be found, you need very little muscle to eat them.
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There's more to life than just "calories". You also need a supply of amino acids to make new proteins (such as enzymes), and if there aren't enough of these in your diet then the only option is to break down muscles or other important tissues. Fat reserves can be used as energy and can even be used to synthesize glucose for the organs that require it, but there's no way to make amino acids from fat.
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This is nonsense.
Your body will burn muscles as the very last resort. In fact it is quite difficult for the body to do so and it needs several weeks of "transforming" to have the necessary enzymes and hormones ready.
No idea why this "burning peptides myth" is so common in our days. Depending on your constitution your body does not even
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That sounds likely if we haven't had supporting evolution of the bone/tendon/etc genes.
My intuition at why we'd have this is slightly different than yours: My first feeling is that it would be likely to be part of the system that controls cancer. (I am not a professional in this area, so take it for what it is worth.)
Eivind.
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The problem is, that there is a huge amount of muscle tissue, but the blood supply is insufficient. Those animals (and humans) are not that much stronger, than normal ones, but their endurance is tremendously lower.
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I wonder what sort of long term side effects you'd be looking at with vastly increased muscle growth.
Side effects: giving wedgies to geeks, and having sex with cheerleaders? Sign me up!
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.
Its just like 'white' mice. How many white mice do you see in the wild? Only escapees I'd bet. I once had an albino chipmunk in my back yard, and he lasted about a week before a hawk caught up with him. He
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More muscle mass equals less flexibility, slower movement,
Incorrect.
inability to climb through small holes.
Maybe. But in nature there isn't a hole a mouse can't dig larger for himself if needed, to crawl through. Having twice the strength would help with that.
I suspect that a mouse being twice as strong wouldn't help it survive simply because strength isn't something that really keeps mice alive. A snake can catch and eat a muscle-bound mouse as easily as a skinny one.
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That's right, if God had intended for us to manipulate genomes He would have given us... actually, that ends rather crudely.
Try this one: If scientists were meant to manipulate genomes they would have won grants by knowing how to use their delicate instruments.
Ah, that didn't go terribly well did it. Let me try a car analogy: there's nothing wrong with taking off the brakes if you have taken alternative steps to achieve proper protection.... Like expert handling or using the stick to really gear down.
Regen
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any tissue that is maintained by a population of resident adult stem cells (like skeletal muscle) can only be maintained through a finite number of adult stem cell divisions. at a certain point the telomeres of the DNA get chopped down too far and those cells that have "overdivided" become quiescent, ie: they won't divide any more. this results in that tissue losing the ability to maintain itself.
so the results of this are interesting, but we can only add this gene to the long list of genes that have been
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Just how wide a tunnel do you think a mouse needs?
Clue: the average house mouse, Mus musculus, is shy of four inches long from the tip of the nose to the base of the tail and normally 2 inches wide. This does not mean that they need a two inch wide tunnel.
I've seen an adult mouse push itself through a hole less than a quarter inch wide. Those little bastards can fold their skulls.
Rats (specifically, norvegicus) are even better. Not only can they squeeze through impossibly small gaps (four pounds of feral ro
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I have this sneaking suspicion that if genome 'brakes' are present in most animals, they're probably there for a reason.
I wonder what sort of long term side effects you'd be looking at with vastly increased muscle growth.
Probably the inability to consume enough food to keep those muscles functioning.
LISP (Score:2)
I kind of giggled at the lab's name(on TFA's video). I don't see enough parentheses on it though.
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I don't see enough parentheses on it though.
Lemme guess, you're a Lisp hacker.
(I keed, I keed!)
Obligatory (Score:1)
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Came for the summary, stayed for the "overlord" comment.
CBS or Man and Machine? (Score:2)
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But if they protest, they could end up with the world's most dangerous rodent infestation.
But the important question is: (Score:2)
Can the NCOR1 "mighty mice" beat up the PEPCK-C "supermice" from 4 years ago?
So they did mice? (Score:2, Interesting)
Belgians thought bigger:
http://en.wikipedia.org/wiki/Belgian_Blue [wikipedia.org]
http://www.youtube.com/watch?v=Nmkj5gq1cQU [youtube.com]
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Different gene expression. Myostatin is what does this to those cows, also check out Wendy the super whippet (sp?) and just search in general for myostatin disorders. There are some people that have disorders related to myostatin expression as well.
Use It or Lose It (Score:4, Interesting)
Seems to me that a whole lot of biological processes follow the "use it or lose it" paradigm. From muscle growth, to brain function and even living itself (get fat and lazy, you die sooner).
So what I'd like to see is research to counter-act that. Instead of a new gene-therapy replacement for steroids, how about something prevents muscle loss even for people who are sedentary? Something to counter-act the "maintenance" requirement to staying fit. That would be really nice.
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Scientists do that research too. Bears (and other hibernating animals) are of particular interest here. But humans are (hopefully) approaching a point where famine is not a significant threat to life, so other solutions like this one could also work even though it may increase the metabolic load (in addition to muscle mass) by causing a larger number of mitochondria and higher cellular respiration. (This article's reference paper). [cell.com]
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Muscle mass does this to some extent, since larger muscles burn more calories at rest. I had a friend in college with a genetic abnormality (it may well have been related to this gene or hormone) who stayed tone and muscular with a sedentary lifestyle. As someone above posted, it could well be that we (and mice) would benefit from such a "condition," but it was perhaps selected against for its high caloric requirements. It could also be that it leads to an enlarged heart and untimely death.
But finally I don't think (Score:1)
it can actually fly [wikipedia.org]!
In other news (Score:2)
After years of giving his lunch money to and getting atomic wedgies from the local bully, Johan has finally developed the gene therapy which will enable him to finally kick some ass.
I wonder.... (Score:2)
...what an elephant with this gene defect would look like.
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Probably exactly like your mother.
Anyone know how this is different from myostatin (Score:1)
Any biologists who can tell me how this is different from what happens when myostatin is blocked? We've known about that protein's regulation of muscle development since 1997.
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IANAB, but...
NCoR1 (nuclear receptor corepressor number 1) is coregulatory protein which (according to this paper) apparently inhibits MEF2 (myocite enhancer factor number 2) and PPAR (peroxisome proliferator-activated receptor) and ERRs (estrogen related receptors). MCoR1 is encoded by the NCOR1 gene. Since it is a co-regulator, blocking the expression of this gene will allow for more MEF2, PPAR, and ERRs activity causing more muscle generation and more mitochondrial activity (according to this paper anyh
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I'm curious how this is related to thyroid hormones. Is the linked article incorrect?
Thanks,
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I'm curious how this is related to thyroid hormones. Is the linked article incorrect?
Thanks,
NCOR1 apparently can be called TRAC-1 (thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1) as described in this wiki article [wikipedia.org]
It is a misnomer to say NCOR1 is a thyroid hormone [wikipedia.org] as I believe the NCOR1 protein really operates on the Thyroid hormone receptors and modulates their response and is thus working in (or near) the muscles in this case, not anywhere near the thyroid.
Oh my poor... (Score:1)
Arnold says (Score:2)
At da Salk Institute for Biological Studies we want to pump....you up!
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Bully Whippets and Mighty Mice (Score:2)
This has been done before with a different knockout gene. Alexandra McPherron and Su Jin-Lee created "mighty mice" by knocking out the MSTN gene [harvard.edu] back in 1997. Same sorts of effects - doubled muscle mass, increased endurance and the like. There is a lot of hope in the muscular dystrophy arena that these types of knockout effects can be replicated via drug delivery mechanisms.
These sorts of mutations also occur naturally. I have a whippet and a naturally occurring mutation occasionally results in a bully whip [nytimes.com]
only problems are (Score:2)
(1) the mice are only black and white, and (2) they can only move at 24 frames per second.
Gee, Brain, what do you want to do tonight? (Score:4, Funny)
The same thing we do every night: Use your super-strength and my wits to take over the world!
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I, for one, welcome our new rodent overlords!
finally... (Score:2)
Humm (Score:2)
OK, now fix the joints. (Score:2)
My arthritic hands are so weak now, it's silly. I have to use an aid to open a bottle most times (it's not funny, I'm 36). If this gets FDA approval I see benefits in rebuilding muscle tissue lost due to atrophy. The problem with arthritis, atrophied muscles are only a symptom which is exacerbated with other conditions such as I had (CTS). Now they need to fix the problem of heavily worn cartilage, and I for one am not much keen on the idea of mechanical replacement. Yay science!