When a biologist is talking about a genetically engineered mouse strain which is a "tool strain", what does that mean? What is the exact definition of a tool strain? What is the difference between a tool strain and any other mouse strain?

Also, how are tool strains connected to recombinase techniques? Does using a recombinase automatically create a tool strain? Or are the properties "tool strain" and "recombinase containing strain" independent from each other?

If it is important, the context is mouse (and possibly other animal) strains used in cancer research.

It would help if you could keep the explanation high-level. I only have high-school biology knowledge and I am trying to make sense of the requirements for a software application for use by biologists.

  • $\begingroup$ It would be helpful if you could quote a section from the instructions to that software because such terms tend to depend on context. $\endgroup$ – Armatus Mar 11 '13 at 12:39
  • $\begingroup$ There are no instructions. I am trying to elicit requirements from a single key user who doesn't "get" set theory. She is talking about several types of tumor models and animal strains, and when she tells me of model types A and B, she is not capable of telling me whether A is a subtype of B, B a subtype of A, both are synonyms, or unrelated. Because she is always thinking in terms of concrete data, she cannot generalize it. And when I try to pry it out with focused questions, she starts contradicting herself. Googling has helped a lot, but with the tool strains, I hit a wall. $\endgroup$ – rumtscho Mar 11 '13 at 12:56
  • $\begingroup$ For what it is worth, she convinced me that "tool strains" and "recombinase strains" are synonyms, and that there are other, unrelated types of strains, like "reporter strains", GE-strains without recombinase, and non-GE strains which may have spontaneous diseases like A/J, or be healthy like FVB/N. Then I found examples of reporter strains having recombinase and concluded that my understanding is wrong. Still don't know whether a strain is considered a "tool strain" in the context of a certain experiment, or whether it is a property of the strain itself. $\endgroup$ – rumtscho Mar 11 '13 at 13:05
  • $\begingroup$ Is there anyone else you can talk to? :) In my mind, recombinase strains could be a subset of tool strains, as a recombinase like Cre mentioned below is certainly a tool for genetic engineering, there are other "tools" that can also be used. $\endgroup$ – MattDMo Mar 11 '13 at 19:27

In extension to shigeta's answer, I could well imagine "tool strains" and "recombinase strains" to be equivalent in the sense that they mean strains of mice whose genome you can easily manipulate.

Cre recombinase is an enzyme which can recombine (effectively insert) genes from a plasmid (which you somehow delivered to the cell) into the cell's genome, if Lox-sites are present (Cre-Lox recombination). This is a very common method of integrating genes into eukaryotic model organisms (i.e. mice).

By tool/recombinase strains they could simply mean mice which express recombinase already, so that you can readily insert your genes into specific cells by delivering a plasmid with the genes on it, and then triggering Cre recombinase in the cells you want to modify in order to integrate the genes into those cells' genome.


Until a better answer shows up...

A tool strain appears to be a mouse strain that is useful for making recombinant mice. It has genes inserted into its genome to make detection of your manipulations easier. In this case several phenotypes (luciferase, human SMN) can be observed as well as a tetracenomycin resistance marker is in place so that offspring with the gene can be easily estimated.

These Tg(SMN2)89; Smn1+/-; Tg(SMNΔ7)4299; ROSA26rtTA; "old" Luci-TRE-SMN mice allow high levels of both luciferase and full-length human SMN expression to be regulated by the addition/removal of doxycycline. These may be useful as a fluorescent reporter and/or Tet-On/Tet-Off tool strain for doxycycline-inducible rescue of Type II (moderate) proximal spinal muscular atrophy (SMA).

  • $\begingroup$ I have always called those reporter mice... $\endgroup$ – nico Mar 11 '13 at 17:37
  • $\begingroup$ its a new term to me as well. Its a big time saver though because you never know when a recombinant mouse gene has bred into a new generation - you'd otherwise have to do a PCR and sequence from each mouse you get. Now you only need to validate a few likely candidates. $\endgroup$ – shigeta Mar 11 '13 at 18:33

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