Archive for the ‘mice’ Category

During the course of research, rodents are commonly euthanized for tissue collection, to end suffering or to terminate surplus animals.  Several methods of euthanasia are possible, and out of these, CO2 euthanasia is most preferred.

An overview of the types of euthanasia available:

Cervical dislocation describes a method in which the head is separated from the spine.  If performed correctly, it can be a quick death.  However, it is technically demanding and any errors would result in suffering by the rodent.  Due to it’s technical nature and the potential for error, it is not a commonly used technique.

Decapitation describes the physical separation of the head from the body.  Some investigators may pursue this method of euthanasia because it does not contaminate the blood or the tissues, which may be of importance in some studies.  While the death itself is quick, again, it relies on the skill of the technician to perform the euthanasia quickly and flawlessly.  Additionally, the handling and restraint required to decapitate a rodent may cause unnecessary stress prior to death.

Chemical methods of euthanasia are generally brought about through the use of lethal injections, typically barbituates. These are generally administered through a subQ injection.  Chemical euthanasia does not require a lot of handling nor technical skill, but some chemicals may be controlled substances or be considered too costly and time consuming to use on large numbers of animals.

Finally, CO2 euthanasia is a form of gaseous euthanasia.  It is the most common form used in laboratory animal science.  It is cheap, requires little to no technical skills, and has some anesthetic properties.  In this form of euthanasia, carbon dioxide is allowed to gradually fill a chamber containing one or more rodents.  As the oxygen levels decline, the animals are rendered unconscious, followed by death from asphyxiation.

While CO2 euthanasia has been the go-to method in recent years, a 2006 thesis by a UBC Animal Welfare Program grad suggests that CO2 euthanasia may cause distress* in rodents due to the dyspnea (the sensation of “breathlessness”) that precedes unconsciousness.   The idea that CO2 euthanasia causes distress in rodents has been explored in other studies as well.

I will note that the UBC Animal Welfare Program does not harm animals used in it’s research nor does it breed animals for the purposes of research.  All animals used are “surplus” from other labs which would have otherwise been euthanized. I will also note that all information provided here is freely available from the above mentioned papers, Wikipedia, and other online sites.

KM Conlee, ML Stephens, AN Rowan and LA King (2005) Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats. Lab Anim 39:137-161.

Lee Niel Ph.D. (2006) “Assessment of distress associated with carbon dioxide euthanasia of laboratory rats” (thesis)


* “Distress” is one of those nebulous, poorly defined words used in animal research.  Much like “ethics”.  ;)  For the purposes of this post, I use “distress” as defined by the author: “… an umbrella term that encompasses negative affect associated with more specific negative states such as pain, discomfort and fear”.

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Hi all,
Just a reminder that CALAS-Pacific has finally gotten around to gracing us with another seminar Wednesday Oct 20 and guess what? It’s a webinar! :p Your member dollars at work…

I think this one is at least somewhat interactive, but I’m not sure. The speakers will be discussing a new technique for measuring oxygen content in mice.

It will be held at the BC Cancer Research Centre at 675 West 10th Ave, Vancouver BC tomorrow from 2:30 – 3:30. Enter from the main doors and head to your right to get to the auditorium.

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Happy (Canadian) Thanksgiving all!

Today was marked by a veritable flood of media attention on the continued UBC animal research debate.  A diverse range of media groups including CBC News, the Vancouver Sun, and online sources presented opinions and stories on the ongoing request for UBC’s animal research data.

Why UBC has not responded with a clear and definite answer is beyond me. Science has benefited so much in the last 10 years thanks to the increase in and availability of open-source platforms. Indeed, many institutions are actively pursuing publication in open source media, due to the incredible increase in journal prices. So why the secrecy with animal experimentation?

It doesn’t help when some animal rights groups still present data from the 1950s and voraciously denounce “vivisection”. Which of course, is followed by scientists denouncing activists as “nutcases” or the like.

In reality, both sides need to move forward, if only for the betterment of animal welfare.

Yes, vivisection is bad. It describes a “live dissection”. But it doesn’t happen in modern research. When tissues are required that can’t be obtained by sampling, the animals are euthanized humanely and then necropsied (AFTER death) for their tissues. To continue to rail against the practice of “vivisection” does not help the cause of animal welfare. True, many groups will continue to use it because it evokes horrific images of cruelty – but do you want to change science for the better, or just inspire mistrust and promote ignorance? (Note: If examples of vivisection can indeed be found in modern research, please castrate the instigators, with my blessing. ;)

Yes, crazy car-bombing family-threatening activists are bad. But that doesn’t describe everyone. Most people just care about animal welfare. Sure there are nut jobs out there, but pick ANY cause and you will find that there are people who like to cause trouble who are drawn to “causes”. That doesn’t mean that the cause itself is bad.

Activists need to be shown that animals are, at the very least, being treated humanely and that animals are only used when absolutely necessary. They need to be able to understand modern scientific data and use examples from modern research to support their causes. I highly recommend some of the research which UBC’s Animal Welfare department has done. For example they have found that the most commonly used method of mouse euthanasia, CO2 asphixiation, may actually be more distressing to mice than originally thought. Disturbing, since it is so widely used.

Scientists need to better understand the ethical concerns raised by activists. They are valid concerns! It is disturbing that so few science majors take philosophy or ethics, because as we have seen in the past, science without morality is a dangerous thing.

I’ll be keeping an eye on the situation as it unfolds. Check back for updates!

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And AGAIN another reason to educate the general public about the realities of biomedical research involving animals – the Vancouver Sun now reports that animal rights activists are getting more curious about the animal-based research at UBC and affiliated hospitals.

I had heard news of this through the grapevine a few weeks ago actually and I’m not surprised it broke popular media. Science does a very poor job of explaining why animals need to be used in research. Often, the only time it gets publicity is when bad things happen. Couple this with the extreme lack of education provided to many animal handlers, the fact that many studies actually shouldn’t be or don’t need to be using animals, and the lack of public education on the issue… you have a bad situation all around.

Part of me is sympathetic. There are a lot of things I don’t agree with when it comes to animal research in Vancouver. When I worked in the field, there were things that definitely should not have happened. And those need to be fixed, without a doubt. Certainly those aspects of research played a big part in my decision to change careers. But at the same time, I understand the reasons for using animals in certain types of research when used correctly and ethically. The sad part is when this does not happen :(

Photo by Dale Tidy

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Like most rodents, mice are prey animals with a range of predators such as urban owls and cats. As a prey species, mice will attempt to hide any signs of distress or pain. In the wild, this is can be a beneficial behaviour because many predators will choose prey which appear weaker or slower than the rest. However, it can also make it difficult to determine the health of your mouse.

A happy and healthy mouse has a sleek coat that is well groomed and tidy. His eyes are bright and alert and his skin is flush slightly pink. When pinched at the scruff, the skin should be elastic and smooth. His body should be filled out and usually slightly plump. When placed in the cup of your hand, the mouse should be curious and attempt to investigate his new surroundings. A mouse that has been well cared for and well acclimatized to humans should not attempt to bite.

An unhappy or distressed mouse many show many or few symptoms. General signs of stress may present itself as a ruffled, ungroomed appearance. The eyes may be dull. This is when you should start taking a closer look at your mouse.

  • She may show other grooming-related symptoms such as an oily coat (eg. diarrhea) or patchy fur (eg. over grooming, ulcerative dermatitis).
  • She may have signs of skin irritation, in the form of reddened areas and inflammed skin (eg. ulcerative dermititis)
  • She may be isolating herself from cagemates. As mice like to hide their discomfort, when it is obvious that a mouse is acting “differently” from the other mice, it is a definite sign that some thing is wrong. When isolation is accompanied by a lethargic appearance and lack of activity, this often indicates that the mouse is in extreme pain or discomfort and should be taken very, very seriously.

If these signs are not noticed immediately, an unhappy mouse may progress to more serious symptoms. For example, the spine may begin to show itself as the mouse loses weight. When pinched at the scruff, the skin might show a “tented” appearance rather than being elasticky – this is a sign of dehydration.

Keep in mind that mice are very little animals and when things go downhill, they can get bad very quickly. Do your mice a favour and keep an eye on them! Things like dehyration or over-grooming should be treated immediately. Stress and over-grooming can often be prevented through gentle handling and adequate environmental enrichment. Give your mice something to chew on other than each other! And finally, if it looks like a mouse might be in pain, realize that he’s probably been in pain for longer than you realized and euthanize the poor little guy.

(And then go revisit your protocol and ask yourself what you can do to prevent this from happening again!)

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I’ve been a bad blogger and have been seriously lacking in posts… :(

I was recently sent an article in New Scientist about lab animal waste in research. I was very happy to see that other people are passionate about reducing unnecessary animal usage in research.

CD1 mouse

Simon makes a number of good points, such as enforcing the use of statistically sound numbers for justifying animal usage and designing experiments which use the minimum numbers of animals most effectively.

Other points I’d suggest:

  • Penalties for labs and researchers who keep excess animals around “just in case”, only to sacrifice them when they become too old for any useful experiments.  I’ve see mice over 2 years old, languishing as “breeders” in animal facilities by labs who have plainly forgotten about them.  Inevitably, once someone finally notices them, these mice are euthanized – wasteful.
  • Restrictions on excess breeding.  Right now, a lab can get away with “justifying” ridiculously high numbers of mice on animal ethics protocols by claiming loss of animals during breeding due to cannibalism or lack of care by the mother.  Why not develop better breeding protocols which nurture mothers and their young rather than having more sub-par breeders?

And finally:

  • Develop a strategy for dealing with excess animals.  On the flip side of bad breeding is the production of excess animals.  Often this occurs when breeding transgenic animals because not all of the animals produced will carry the transgene.  Usually, these “extra” animals are euthanized.  I’d like to see a comprehensive strategy which would funnel these animals into a purpose -  As controls in an experiment? In teaching?  Pet food for snakes, etc?

Good article, and great to see an important issue addressed.


Small rant: Little bothers me more about animal research than seeing animals purposely bred and then discarded.  It’s the one aspect of animal research that I have never found moral justification for – How can you justify bringing a living thing into the world, only to throw it away because it does not suit your specifications?

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Earlier this month, I wrote about a recent paper which looked at creating a “pain scale” based on the facial expressions of mice. I finally got around to reading the actual published paper.

Here’s the reference: Langford, DJ et al. Nature (2010). Some interesting things I noted:

“Causing headaches in mice”
This one made me blink when I read it in a news release. How can you claim to cause headaches in mice when your study is looking at how to classify pain in mice? Well, apparently, some of the mice used were transgenics which carried a gene linked to familial hemiplegic migraine in humans. These mice seemed to exhibit a baseline level of pain, presumably due to the transgenic gene they carry. I wouldn’t say that’s equivalent to “causing mice headaches” but hey, I don’t write for newspapers.

They measured what?!
When I read the news releases, I was under the impression that lots of fancy imaging software was being used, that microscopic twitches and fine-detail facial expressions were being mapped, and in general, crazy stuff was going on. How wrong I was! The original article included representative images used to rate different levels of mouse pain. For each trait, there were three images. Images set to a scale of 1 to 3 – 1 being “normal” and 3 being “severe pain”. After looking at the pictures, I had a “And this needed to be a scientific study… why?” moment. For example, under “orbital tightening”, there was a normal mouse, a slightly squinty mouse, and a mouse whose eyes were dry and narrowed to slits. Any animal technician would (or at least, should) be able to tell you that the mice in the #3 category were in pain and that the animals in the #2 category were not doing well.

But, to be fair, it is true that recognizing and using something daily is not the same as having a defined, well-studied scale to refer to. If making an official scale helps animal care, I’m all for it. To be honest, I’m a little surprised that a scale as not been officially developed (studied and peer reviewed) before, considering that the majority of animal facilities use some sort of point-scale for rating animal health.

Looking forward to hearing more from this group. Hopefully they’ll go into some more applications next time.

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In a collaboration between UBC and McGill researchers, a study was very recently published in Nature Methods which looks to quantify pain based on facial expressions in mice. The study has since been popularly named the “Mouse Grimace Study” in popular media, such as the local Vancouver Sun and online at Science Daily.

I can’t seem to get access to the full journal article at the moment, but from what I’ve read, the study investigators injected mice with solutions containing varying levels of irritant. They suggest that the pain level is somewhat similar to a headache. I’m a bit skeptical at that assertion – how can you claim to cause a headache in a mouse, when your study is trying to measure pain response in the first place?

I would guess that the injections are actually more similar in discomfort level to a human receiving a vaccination. As most people probably have observed, some vaccinations are more painful than others, depending on the salinity and contents. (Side note – received a new vaccination of MMR a few months ago at the insistence of my employer… MMR = liquid pain)

After injecting the mice, the authors used some fancy imaging to record things like, ear position, whisker twitches and eye movement. The results of these images are compiled into a scale based on the pain intensity of the injected solution. So, theoretically, the “mouse grimace scale” could be used to determine how much pain a mouse is in.

It’s important to note that the authors are looking at mild pain stimuli, not moderate (eg. fight wound, superficial surgery, etc.) or high (eg. invasive surgery, broken limb, etc.) levels of pain.

Granted, I haven’t read the entire paper yet, but as someone who’s worked with animals, I’m a little skeptical about measuring mouse facial expressions as a response to mild pain stimuli. Ear twitches could be in response to sound, perhaps at a frequency the authors do not detect. Blinking could be a result dryness in the eyes after being whisked out of a cage and then dropped back in, perhaps too quickly.

It should be interesting to read the actual article. Can’t trust popular media any more than you can trust scientists! I’m heading out to the university in a bit, so perhaps I’ll be able to download a copy there.

[Photo by Dale Tidy]

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Personally, I think nude mice are super-cute!

Nude mice, commonly used in research, are instantly identifiable by their hairless, wrinkled pink forms.  Sometimes called “athymic”, due to their lack of a functional thymus, nude mice are also immunodeficient and do not produce T cells.  But how do immunodeficiency and hairlessness relate?

Nude mice have a mutation in a gene called FOXN1.  This gene encodes a transcription factor, which is a protein that is required to activate a gene.  In this case, FOXN1 normally encodes a protein which activates a gene involved in the differentiation of a type of cell called epithelium.

Epithelial cells are cells which form body surfaces, such as skin, and glands, such as the thymus.  Normal development of epithelial cells results in skin with hair and a functional, T cell producing thymus.

The mutation in FOXN1 disrupts the normal development of both skin progenitor cells and thymus progenitor cells.  This results in skin which forms without hair and a non-functional thymus.  And there you go!  A nude, immunodeficient mouse!

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Albino… mouse?

Albinos are a result of genetic abnormalities, usually the possession of two recessive genes for albinism.  Recessive genes are usually not a problem – chances are, everyone has at least a few.  But, when you happen to inherit two, interesting things can result.  Albinism is one of them.

Albino mice show characteristics typical of albinism in general: lack of pigment and red-tinted eyes.  They’re commonly used in biomedical research in the form of mouse strains such as CD1.  In the wild, many albino animals don’t survive due to their lack of camouflaging pigment.  But, some persist and a notable few have an almost cult-like status.

So why choose a genetic abnormality as the name for a science blog?

Well, science is quirky.  Is there anything normal about spending your day mixing chemicals and cells in a dish and then counting them?  I think not.  There is a very high probability of failure – just ask any grad student.  But when the stars align, the supervisor is happy and the antibody works… interesting things can happen.

And hey, if it works for grad students – Who knows what might happen here.  :)

[Photo by Dale Tidy]

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