Gene editing in cell lines can be used to confirm animal models of infection

Lead researcher

Dr Michael Gantier

Main finding

In this work we observed a strong protection of the genetically modified mouse line we were studying against infection by a common type of bacteria causing food poisoning (Salmonella). While attempting to understand the mechanism at play, we discovered that immune cells from these mice exhibited a mutation which should not have been there. Since this mutation had been shown to play a critical role in responses to Salmonella infection, we performed experiments to tease apart the effect from our gene versus that of this unwanted mutation. For this purpose, we relied on gene editing of immune cell lines, in vitro. Our findings indicate that our gene of interest does not contribute to Salmonella infection, and illustrate how gene editing of cell lines can complement experiments relying on genetically modified animals.

Centre

Centre for Innate Immunity & Infectious Diseases

Research group

Nucleic Acids and Innate Immunity

Co-authors

Ferrand J, Croft NP, Pépin G, Diener KR, Wu D, Mangan NE, Pedersen J, Behlke MA, Hayball JD, Purcell AW, Ferrero RL, Gantier MP.

Journal and article title

Most surprising

We discovered that the genetically modified mouse line we were using contained a "background" mutation, originating from the way the mice were generated - which was accountable for the protection against Salmonella infection we originally observed.

Future implications

This works underlines the importance of using various complementary approaches to study gene function in infection models, to avoid results misinterpretation.
With several simple approaches now available to study gene function (e.g. gene editing, RNA interference, or antisense), it should now become standard practice to confirm results from older animal genetic models with in vitro assays to rule out potential mutations introduced when generating the animals (which are most often not accounted for by researchers).

Disease/health impact

Bacterial infection

Dr Michael Gantier from the Nucleic Acids and Innate Immunity Research Group at Hudson Institute