Hypothesis
MERTK in endothelial cells maintains barrier function and restrains neutrophil transendothelial migration, so deleting it specifically in endothelium should aggravate inflammatory lung injury.
What failed
Knocking MERTK down in primary human pulmonary microvascular endothelial cells increased neutrophil transmigration and dextran leak and disrupted adherens junctions and basal Rac1 activity, and global Mertk-null mice recruited more neutrophils and leaked more Evans blue during Pseudomonas aeruginosa pneumonia. But inducible endothelium-specific Mertk-null mice showed no difference from controls in either neutrophil migration into inflamed lungs or vascular permeability.
Broken assumption
A global knockout phenotype localises to the cell type that reproduces it in culture.
Why
The authors report that selective deletion in endothelial cells in vivo failed to reproduce the response seen in culture and in the global knockout, without identifying the compensating cell type.
From the published paper: Li et al. PLoS ONE, 2019. ↗CC BY