UC San Diego

The loss of the gene membrane-bound O-acyltransferase 7 (MBOAT7) is associated with intellectual disability, seizures, and autism-like features in humans [OMIM 606048]. MBOAT7 codes for the protein lysophosphatidylinositol acyltransferase 1 (LPIAT1), which preferentially esterifies arachidonoyl-CoA to the Sn2 position of lysophosphatidylinositol, generating the predominant 20:4 containing species of phosphatidylinositol. Here we show that the knockout of Mboat7 causes spatially and temporally restricted cell death in the embryonic murine neocortex, leading to disrupted radial glia patterning and diminished cortical thickness. We also show a significantly altered lipidome in both Mboat7 knockout mice and human neural tissue, as well as a dynamic equilibrium of lipid species in differentiating patient derived neural progenitor cells. We hypothesize that these characteristics contribute to the encephalopathies of MBOAT7 patients.