Investigation of the fatty acid transporter-encoding genes SLC27A3 and SLC27A4 in autism

• Project/Area Number: 15K15436
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: YOSHIKAWA TAKEO 国立研究開発法人理化学研究所, 脳科学総合研究センター, チームリーダー (30249958)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 自閉症 / 脂肪酸 / 脂肪酸トランスポーター / FATP3 / FATP4 / iPS / bEnd3細胞 / BODIPY / in silico構造解析

Outline of Final Research Achievements

The FATP gene family encodes fatty acid transport proteins. We investigated functional abnormalities of FATP genes in terms of the pathogenesis of autism spectrum disorders (ASD). We confirmed the expression of FATP3 and FATP4 in human neural stem cells derived from iPS cells, which suggested their involvement in the developmental stage of the central nervous system. Additionally, we resequenced the FATP3 and FATP4 genes using 267 ASD patient and 1140 control samples and detected 47 and 30 variants for the FATP3 and FATP4, respectively, revealing that they are highly polymorphic with multiple rare variants. The FATP4 Ser209 allele was more frequently represented in ASD samples. We showed that a FATP4 Ser209 mutant resulted in significantly higher fluorescently-labeled fatty acid uptake into bEnd3 cells, a mouse brain capillary-derived endothelial cell line, compared with FATP4 Gly209, suggesting that the functional change may contribute to ASD pathophysiology.

Research Products

• [Journal Article] Investigation of the fatty acid transporter-encoding genes SLC27A3 and SLC27A4 in autism. (2015)
  • Author(s): Maekawa M, Iwayama Y, Ohnishi T, Toyoshima M, Shimamoto C, Hisano Y, Toyota T, Balan S, Matsuzaki H, Iwata Y, Takagai S, Yamada K, Ota M, Fukuchi S, Okada Y, Akamatsu W, Tsujii M, Kojima N, Owada Y, Okano H, Mori N, Yoshikawa T
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 16239-16239
  • DOI: 10.1038/srep16239
  • Peer Reviewed / Open Access / Acknowledgement Compliant