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 Takai, Tsuyoshi Miyakawa, Takuya Kitamura, Akio Kihara

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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
Volume33
Issue number1
DOIs
Publication statusPublished - 01-01-2019

Fingerprint

Sjogren-Larsson Syndrome
Gene Knockout Techniques
long-chain-aldehyde dehydrogenase
Knockout Mice
Brain
Genes
Myelin Sheath
Lipids
Sphingolipids
Pathology
Mixed Function Oxygenases
Metabolism
Neurons
Insulation
Fatty Acids
Oligodendroglia
Tissue
Nervous System Diseases
Lipid Metabolism
Action Potentials

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Kanetake, Tsukasa ; Sassa, Takayuki ; Nojiri, Koki ; Sawai, Megumi ; Takai, Satoko ; Miyakawa, Tsuyoshi ; Kitamura, Takuya ; Kihara, Akio. / Neural symptoms in a gene knockout mouse model of Sjogren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide. In: FASEB Journal. 2019 ; Vol. 33, No. 1. pp. 928-941.
@article{41a011fda01a4b8198c32b427564f41b,
title = "Neural symptoms in a gene knockout mouse model of Sjogren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide",
abstract = "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.",
author = "Tsukasa Kanetake and Takayuki Sassa and Koki Nojiri and Megumi Sawai and Satoko Takai and Tsuyoshi Miyakawa and Takuya Kitamura and Akio Kihara",
year = "2019",
month = "1",
day = "1",
doi = "10.1096/fj.201800291R",
language = "English",
volume = "33",
pages = "928--941",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "1",

}

Neural symptoms in a gene knockout mouse model of Sjogren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide. / Kanetake, Tsukasa; Sassa, Takayuki; Nojiri, Koki; Sawai, Megumi; Takai, Satoko; Miyakawa, Tsuyoshi; Kitamura, Takuya; Kihara, Akio.

In: FASEB Journal, Vol. 33, No. 1, 01.01.2019, p. 928-941.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neural symptoms in a gene knockout mouse model of Sjogren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide

AU - Kanetake, Tsukasa

AU - Sassa, Takayuki

AU - Nojiri, Koki

AU - Sawai, Megumi

AU - Takai, Satoko

AU - Miyakawa, Tsuyoshi

AU - Kitamura, Takuya

AU - Kihara, Akio

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85059241498&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059241498&partnerID=8YFLogxK

U2 - 10.1096/fj.201800291R

DO - 10.1096/fj.201800291R

M3 - Article

C2 - 30085884

AN - SCOPUS:85059241498

VL - 33

SP - 928

EP - 941

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 1

ER -