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Journals publishing mouse models with no phenotype - (Oct/27/2011 )

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Hi all,
We made a knockout mouse line, but unfortunately didn’t find any phenotype. We want to publish our negative data anyway and close this project. Would you suggest which journals we should go?
I heard that Genesis may accept this kind of study. Any other suggestions are so much appreciated. Thank you!
B

-BSA2011-

I'm surprised it took so long for someone to answer this. Try PLOS One. They will publish your work if it is supported by the data:

http://www.plosone.org/static/publication

 

Other journals like F1000 Research are making a big push to publish negative data.

 

Sometimes the phenotype takes a while to emerge. Try asking postdocs from around the world to come and study your knockout mouse. I'm sure each one will find a phenotype (positive data) and will publish an article.

-doxorubicin-

 I learned sometime a few months ago.

All knock out mice may actually have a phenotype, you just need to find the right circumstance to see it. And that set of circumstances can be quite exacting. I can't quite remember the details but the story was about this DNA repair protein, a knock out mouse would only show an effect if treated with a specific DNA damaging drug and kept for an additional 30-45 days, after which the mice would start dying from heart attacks. Only the heart muscles were damaged from the drug and unable to repair themselves. Other tissues were unaffected.

 

The research team found this bizarre set of circumstances when they made the mouse knock out and found nothing. Then started looking for human knock out of the gene, focusing on any increase frequency of cancer. They didn't find any increase in cancer but they did discover that those people with this mutation that where treated for cancer has an increase frequency of dying from a heart attack 5-10 years after treatment. They then when back to the mice and treated said mouse with the drug and waited. Then the mice started dying.

-perneseblue-

That's very interesting. Could you post which paper it was if you remember sometime ?

-Tabaluga-

That's very interesting. Could you post which paper it was if you remember sometime ?

 

I will try looking. I don't know if I can find it again. I will try to see if I saved it in my file of interesting stuff. 

I just remember this story only because of the rather exacting circumstances needed to see an effect on a knock out mouse. It required a drug challenge, was tissue specific and needed time for the damage to become pathological.

-perneseblue-

Just on a side note, an interesting topic: http://www.biotechniques.com/news/biotechniquesNews/biotechniques-348564.html

-pito-

@perneseblue: I wonder if you (or anybody else) found it in the meantime ? Just asking because I'm currently writing an essay, and this example would come in handy but of course I'd need more details and a citation.

I'm also looking for it now via google, so far didn't find it but will of course report back if I do.

 

Thanks.

-Tabaluga-

perhaps a paper like this one: http://bfg.oxfordjournals.org/content/6/2/91.abstract might help?

+ keep in mind the paper I also mentioned above...

 

@perneseblue: I wonder if you (or anybody else) found it in the meantime ? Just asking because I'm currently writing an essay, and this example would come in handy but of course I'd need more details and a citation.

I'm also looking for it now via google, so far didn't find it but will of course report back if I do.

 

Thanks.

-pito-

Thanks. This paper was a good one, found some interesting stuff in there as well as in this article: http://www.nature.com/nature/journal/v415/n6867/full/415008a.html

And if someone other than me ever needs to write about that, there are also some nice quotes by Mario Capecchi, Anne McLaren and Lewis Wolpert on the matter. (I mean, if I understand correctly, that all ko mice do have a phenotype is just a hypothesis, and one that's difficult (impossible?) to prove, even though it's very likely. Apparently there are these big mouse phenotyping projects at the moment that try to clear up matters).

All in all a very interesting subject...

-Tabaluga-

I think that stating that ALL ko mice have a phenotype is a bit harsh... on the other hand: I do strongly agree that the chances are very very high that we miss a lot of the phenotypes just because we don't test in the correct parameters (different temp, different time (length of checking) , different food.... stuff like that...) Everything is based on "standard" parameters while this is actually a biased system (I mean: nature vs what we do in a lab...... )

 

 

Not to mention phenotypes in the Xthe generation... (I mean genes that are important for imprinting for example.... )

 

 

Thanks. This paper was a good one, found some interesting stuff in there as well as in this article: http://www.nature.com/nature/journal/v415/n6867/full/415008a.html

And if someone other than me ever needs to write about that, there are also some nice quotes by Mario Capecchi, Anne McLaren and Lewis Wolpert on the matter. (I mean, if I understand correctly, that all ko mice do have a phenotype is just a hypothesis, and one that's difficult (impossible?) to prove, even though it's very likely. Apparently there are these big mouse phenotyping projects at the moment that try to clear up matters).

All in all a very interesting subject...

-pito-
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