@article{6a924373c1ab4994a8dd34c65d41497b,
title = "Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms",
abstract = "Chung et al. show that ACOX1, a peroxisomal protein required for degrading VLCFA, is mostly expressed in glial cells. Its loss causes an accumulation of VLCFA and glial loss. An ACOX1 gain-of-function mutation identified in three individuals leads to elevated ROS and glial loss and is potently suppressed by antioxidants.",
keywords = "ACOX1 deficiency, Drosophila, NACA, ROS, Schwann cells, antioxidant NACA, axonal dystrophy, fatty acid peroxidation, very long chain fatty acids, wrapping glia",
author = "{Members of Undiagnosed Diseases Network} and Chung, {Hyung lok} and Wangler, {Michael F.} and Marcogliese, {Paul C.} and Juyeon Jo and Ravenscroft, {Thomas A.} and Zhongyuan Zuo and Lita Duraine and Sina Sadeghzadeh and David Li-Kroeger and Schmidt, {Robert E.} and Alan Pestronk and Rosenfeld, {Jill A.} and Lindsay Burrage and Herndon, {Mitchell J.} and Shan Chen and Amelle Shillington and Marissa Vawter-Lee and Robert Hopkin and Jackeline Rodriguez-Smith and Michael Henrickson and Brendan Lee and Moser, {Ann B.} and Jones, {Richard O.} and Paul Watkins and Taekyeong Yoo and Soe Mar and Murim Choi and Bucelli, {Robert C.} and Shinya Yamamoto and Lee, {Hyun Kyoung} and Prada, {Carlos E.} and Chae, {Jong Hee} and Vogel, {Tiphanie P.} and Bellen, {Hugo J.}",
note = "Funding Information: We thank Karen Schulze for editing of the manuscript, and Drs. Alex Sweeney and Kevin Baszis for clinical expertise. We thank Hongling Pan and Yuchun He for injections to create transgenic flies. H.K.L. is supported by NMSS via RG1508-08406. M.F.W. S.Y. and H.J.B. are supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director under award numbers U01HG007709 and U54NS093793 and by ORIP via R24OD022005. Confocal microscopy was performed in the Neurovisualization core of the BCM IDDRC (supported by NICHD U54HD083092). P.C.M. is funded by CIHR (MFE-164712). Drosophila stocks were obtained from the Bloomington Stock Center (NIH P40OD018537) at Indiana University. Monoclonal antibodies were obtained from the Developmental Studies Hybridoma Bank, created by the NICHD, and maintained at The University of Iowa. H.J.B. is an Investigator of the Howard Hughes Medical Institute. T.A.R. is supported by The Cullen Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. H.C. M.F.W. T.P.V. and H.J.B. conceived and designed the project. H.C. designed and conducted most experiments and analyzed the data. P.C.M. and S.S. performed the behavioral assays in fly, and H.C. J.J. and H.K.L. designed and performed the primary Schwann cells experiments. T.A.R. performed the immunohistochemistry in fly brain. H.C. Z.Z. and L.D. performed TEM experiments. D.L.K. and H.C. generated dACOX1ywg. M.J.H, R.E.S, A.P. and R.C.B. performed Toluidine staining and TEM analysis. H.C. J.A.R. L.B. S.Y. M.F.W. S.C. B.L. S.M. and T.P.V. collected and analyzed clinical and genomic data of patient 1. T.Y. J.C. and M.C. collected and analyzed clinical and genomic data of patient 2. A.S. M.V. R.H. J.R. and M.H. collected and analyzed clinical and genomic data of patient 3. A.B.M. R.O.J. and P.W. performed lipidomic profiling and analysis. H.C. M.F.W. T.P.V. and H.J.B. wrote the manuscript. The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing conducted by Baylor Genetics Laboratories. Funding Information: We thank Karen Schulze for editing of the manuscript, and Drs. Alex Sweeney and Kevin Baszis for clinical expertise. We thank Hongling Pan and Yuchun He for injections to create transgenic flies. H.K.L. is supported by NMSS via RG1508-08406 . M.F.W., S.Y., and H.J.B. are supported by the NIH Common Fund , through the Office of Strategic Coordination/Office of the NIH Director under award numbers U01HG007709 and U54NS093793 and by ORIP via R24OD022005 . Confocal microscopy was performed in the Neurovisualization core of the BCM IDDRC (supported by NICHD U54HD083092 ). P.C.M. is funded by CIHR ( MFE-164712 ). Drosophila stocks were obtained from the Bloomington Stock Center ( NIH P40OD018537 ) at Indiana University. Monoclonal antibodies were obtained from the Developmental Studies Hybridoma Bank, created by the NICHD, and maintained at The University of Iowa. H.J.B. is an Investigator of the Howard Hughes Medical Institute. T.A.R. is supported by The Cullen Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2020",
year = "2020",
month = may,
day = "20",
doi = "10.1016/j.neuron.2020.02.021",
language = "English",
volume = "106",
pages = "589--606.e6",
journal = "Neuron",
issn = "0896-6273",
number = "4",
}