Mfsd2a, a member of the major facilitator superfamily, is a sodium-dependent lysophosphatidylcholine (LPC) transporter. It is crucial for the uptake of docosahexaenoic acid (DHA), an essential omega-3 fatty acid, into the brain, which is vital for normal brain growth, cognitive function, and maintaining the integrity of the blood-brain barrier (BBB) [2,3,4,5]. It is also involved in lipid metabolism pathways [1]. Genetic models, such as knockout (KO) mouse models, have been instrumental in studying its functions.

In Mfsd2a-deficient (Mfsd2a-knockout) mice, there is a marked reduction in DHA levels in the brain, accompanied by neuronal cell loss in the hippocampus and cerebellum, cognitive deficits, severe anxiety, and microcephaly [2]. These mice also have a leaky BBB from embryonic stages to adulthood due to increased CNS-endothelial-cell vesicular transcytosis, despite normal vascular network patterning [3]. In the context of acute kidney injury (AKI), Mfsd2a haploinsufficient mice exhibit delayed renal function recovery, with histological markers of damage, fibrosis, and inflammation, along with a deficiency in DHA-containing phospholipids [6].

In conclusion, Mfsd2a is essential for normal brain development, cognitive function, and BBB integrity, as well as renal recovery after AKI. Studies using Mfsd2a KO mouse models have revealed its role in these biological processes, highlighting its potential as a therapeutic target for diseases related to the nervous system and kidney [2,3,6].

References:

1. Zhang, Bin, Wang, Chun-Mei, Wu, Hao-Xiang, Xu, Rui-Hua, Cao, Xue-Tao. 2023. MFSD2A potentiates gastric cancer response to anti-PD-1 immunotherapy by reprogramming the tumor microenvironment to activate T cell response. In Cancer communications (London, England), 43, 1097-1116. doi:10.1002/cac2.12476. https://pubmed.ncbi.nlm.nih.gov/37539769/

2. Nguyen, Long N, Ma, Dongliang, Shui, Guanghou, Goh, Eyleen L K, Silver, David L. 2014. Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. In Nature, 509, 503-6. doi:10.1038/nature13241. https://pubmed.ncbi.nlm.nih.gov/24828044/

3. Ben-Zvi, Ayal, Lacoste, Baptiste, Kur, Esther, Yan, Han, Gu, Chenghua. 2014. Mfsd2a is critical for the formation and function of the blood-brain barrier. In Nature, 509, 507-11. doi:10.1038/nature13324. https://pubmed.ncbi.nlm.nih.gov/24828040/

4. Wong, Bernice H, Silver, David L. . Mfsd2a: A Physiologically Important Lysolipid Transporter in the Brain and Eye. In Advances in experimental medicine and biology, 1276, 223-234. doi:10.1007/978-981-15-6082-8_14. https://pubmed.ncbi.nlm.nih.gov/32705603/

5. Huang, Bei, Li, Xihong. 2021. The Role of Mfsd2a in Nervous System Diseases. In Frontiers in neuroscience, 15, 730534. doi:10.3389/fnins.2021.730534. https://pubmed.ncbi.nlm.nih.gov/34566571/

6. Loke, Randy Y J, Chin, Cheen Fei, Liang, Gao, Torta, Federico, Silver, David L. 2023. Mfsd2a-mediated lysolipid transport is important for renal recovery after acute kidney injury. In Journal of lipid research, 64, 100416. doi:10.1016/j.jlr.2023.100416. https://pubmed.ncbi.nlm.nih.gov/37467896/