Neural symptoms in a gene knockout mouse model of Sjögren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide.
Insulation by myelin lipids is essential to fast action potential conductivity: changes in their quality or amount can cause several neurologic disorders. Sjögren-Larsson syndrome (SLS) is 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 neurons in the mouse brain, and neurons of Aldh3a2 knockout (KO) mice exhibited impaired metabolism of the long-chain 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.-Kanetake, T., Sassa, T., Nojiri, K., Sawai, M., Hattori, S., Miyakawa, T., Kitamura, T., Kihara, A. Neural symptoms in a gene knockout mouse model of Sjögren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide.
['Kanetake|Tsukasa|T|', 'Sassa|Takayuki|T|', 'Nojiri|Koki|K|', 'Sawai|Megumi|M|', 'Hattori|Satoko|S|', 'Miyakawa|Tsuyoshi|T|', 'Kitamura|Takuya|T|', 'Kihara|Akio|A|']
D000445:Aldehyde Oxidoreductases D000818:Animals D001007:Anxiety D001522:Behavior, Animal D003863:Depression D005699:Galactosylceramides D006801:Humans D008027:Light D050356:Lipid Metabolism D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009043:Motor Activity D016111:Sjogren-Larsson Syndrome
myelin aldehyde ALDH3A2 sphingolipid fatty acid 2-hydroxylase