A researcher wants to create a mouse model for a disease, to allow her team to study possible therapies. The disease is known to be caused by a small deletion that removes a certain gene. Which type of mouse would be the best choice for this purpose?

Question

A.  Knockout mouse
B.  Knockin mouse
C.  Conditional knockout mouse activated by a drug
D.  Mutant derived by traditional forward genetics screen
E.  Tissue-specific gene knockout

Clarify Question  
· What is the key concept addressed by the question?
· What type of thinking is required?

  Gather Content
· What do you already know about transgenic mouse technology?

  Choose Answer
· Given what you now know, what information and/or problem solving approach is most likely to produce the correct answer?
   Reflect on Process  
· Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?

Answer 1

A.  Knockout mouse

Clarify Question  
· What is the key concept addressed by the question?
         o This question addresses transgenic mouse technology.
· What type of thinking is required?
        o This question is asking you to weigh and judge evidence, or evaluate, to choose the best of the possible answers.

  Gather Content
· What do you already know about transgenic mouse technology?
        o The knockout mouse technique creates a loss-of-function of the target gene by inserting a neomycin cassette.
        o The knockin mouse replaces the normal gene with a modified version created by the experimenter.
        o The conditional knockout mouse removes the gene using Cre-lox, but only after treating the animals with a drug. This allows removal of the gene after a certain amount of development.
        o The tissue-specific gene knockout mouse removes the gene using Cre-lox, but only in specific tissues in which Cre is active. This allows removal of the gene in a subset of tissues.
        o A mutant mouse can be derived by a traditional forward genetics screen, but this is expensive and arduous, and not guaranteed to work. This is especially difficult if the mutant would be sickly or lethal, or if the phenotype is unknown.

  Choose Answer
· Given what you now know, what information and/or problem solving approach is most likely to produce the correct answer?
        o Given that the experimenter wants to mimic a loss-of-function of a gene throughout the body, the best approach would be to create a knockout mouse.
        o Doing a traditional screen is too uncertain and expensive.
   Reflect on Process  
· Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?
        o The question required you to weigh and judge evidence, or evaluate, to choose the best of the possible answers.
        o Did you recognize that the knockout mouse is the best choice, because it mimics the disease, but is easier to create than doing a genetics screen?