Transportability of mouse gene knockout models to human complex phenotypes

In 30 matched mouse–human phenotype pairs, GPAT found transportability for 12 mouse phenotypes, with meta-analysis showing positively correlated genome-wide perturbation effects (P = 2.3x10-27).

• Why it matters: Mouse knockout results are useful for human disease biology, but only translate when the same gene perturbations shift corresponding human phenotypes in the same direction.
• What they did: The study combined International Mouse Phenotyping Consortium mouse perturbation data with UK Biobank predicted loss-of-function data using the GPAT framework across 30 matched phenotype pairs.
• The result: Transportability was supported for biochemical, cellular, and anthropometric phenotypes, while fat mass and body mass index showed limited evidence under murine conditions; mouse glucose measurements had some evidence for diabetes mellitus.

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