Study of vascular endothelial-specific and inducible vascular endothelial-specific deletion of Major Facilitator Superfamily Domain containing 2a (Mfsd2a) in mice.. Study of vascular endothelial-specific and inducible vascular endothelial-specific deletion of Major Facilitator Superfamily Domain containing 2a (Mfsd2a) in mice.

Brain development requires a massive increase in brain lipogenesis and accretion of the essential omega-3 fatty acid docosahexaenoic acid (DHA). Brain acquisition of DHA is primarily mediated by the transporter Major Facilitator Superfamily Domain containing 2a (Mfsd2a) expressed in the endothelium of the blood-brain barrier. Mfsd2a transports DHA and other polyunsaturated fatty acids esterified to lysophosphatidylcholine (LPC-DHA). However, the function of Mfsd2a and DHA in brain development is incompletely understood. Using vascular endothelial-specific (2aECKO) and inducible vascular endothelial-specific (2aiECKO) deletion of Mfsd2a in mice, we found Mfsd2a to be uniquely required postnatally at the blood-brain barrier for normal brain growth and DHA accretion, with DHA deficiency preceding the onset of microcephaly. Gene expression profiling analysis of these DHA deficient brains indicated that Srebp-1 and Srebp-2 pathways were highly elevated. Affymetrix gene arrays were used to determine differences in gene expression between 2aECKO or 2aiECKO relative to their respective controls in the developing brain. Overall design: RNA was extracted from half cerebrums of postnatal day 8-9 2aECKO, 2aiECKO or Mfsd2afl/fl mice. Equal amounts of RNA was pooled from five to six half cerebrums per genotype. Microarray profiling was done on pooled samples with a RIN cut-off of 8.0 using Mouse 430 2.0 arrays (Affymetrix).