Neural symptoms in a gene knockout mouse model of Sjogren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide

Tsukasa Kanetake, Takayuki Sassa, Koki Nojiri, Megumi Sawai, Satoko Hattori, Tsuyoshi Miyakawa, Takuya Kitamura, Akio Kihara

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Insulation by myelin lipids is essential to fast action potential conductivity: changes in their quality or amount can cause several neurologic disorders. Sjogren-Larsson syndrome (SLS) i s one such disorder, which is caused by mutations in the fatty aldehyde dehydrogenase ALDH3A2. To date, the molecular mechanism underlying SLS pathology has remained unknown. In this study, we found that Aldh3a2 is expressed in oligodendrocytes and neuronsinthemouse brain, and neurons of Aldh3a2knockout (KO)mice exhibitedimpaired metabolism ofthelongchain base, a component of sphingolipids. Aldh3a2 KO mice showed several abnormalities corresponding to SLS symptoms in behavioral tests, including increased paw slips on a balance beam and light-induced anxiety. In their brain tissue, 2-hydroxygalactosylceramide, an important lipid for myelin function and maintenance, was reduced by the inactivation of fatty acid 2-hydroxylase. Our findings provide important new insights into the molecular mechanisms responsible for neural pathogenesis caused by lipid metabolism abnormalities.

Original languageEnglish
Pages (from-to)928-941
Number of pages14
JournalFASEB Journal
Issue number1
Publication statusPublished - 01-2019


All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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