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How should a PI justify the use of vertebrate species when asked about invertebrate alternatives?

As part of his most recent IACUC submission, Dr. John Tuckerton requested the use of 40 C57Bl/6 mice to determine the most effective in vivo dose of P4484-17, a newly synthesized molecule that, in vitro, exhibited strong inhibition of prostaglandin E2 (PGE2). PGE2 is an activator of the Wnt signaling pathway, a protein-based pathway that can impact embryonic development. The experimental design was to test three dose levels of P4484-17, with ten mice per dose level and one group of ten untreated control mice. Based on the dose that led to the greatest inhibition of PGE2 in the mice, Tuckerton would initiate a much larger study of the Wnt pathway and embryonic development. The larger study involved nearly 1000 mice and examined multiple aspects of mouse embryonic development, with a focus on how the longitudinal (anteroposterior) axis of the body developed.

One of the reviewers of Tuckerton's protocol submission was Dr. Andrea McCarthy, a geneticist who was aware that there was a Wnt signaling pathway in fruit flies. One of her written questions to Tuckerton was: Can this study be performed in fruit flies? Tuckerton responded that his goal was to be able to translate his work on mouse development to human development and therefore, in his opinion, using an invertebrate model was not appropriate.

Do you think that Tuckerton's answer to McCarthy's question was sufficient to justify his use of mice? Whether you agree or disagree with Tuckerton's response, what additional questions would you ask of Tuckerton, based on the limited information presented in this scenario?

Response to Protocol Review Scenario: It's all in the questions

Response to Protocol Review Scenario: A need for more justification

Response to Protocol Review Scenario: If it's only an opinion, it won't fly

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Silverman, J. How should a PI justify the use of vertebrate species when asked about invertebrate alternatives?. Lab Anim 46, 319 (2017). https://doi.org/10.1038/laban.1317

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