A mouse model for intellectual disability caused by mutations in the X-linked 2'‑O‑methyltransferase Ftsj1 gene.

Autor: Jensen LR; Department of Functional Genomics, Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Felix-Hausdorff-Strasse 8, 17489 Greifswald, Germany. Electronic address: jensenl@uni-greifswald.de., Garrett L; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany., Hölter SM; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany., Rathkolb B; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-University München, Feodor-Lynen Str. 25, 81377 München, Germany; German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany., Rácz I; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, Sigmund Freud Str. 25, 53127 Bonn, Germany; Clinic of Neurodegenerative Diseases and Gerontopsychiatry, University of Bonn Medical Center, Bonn, Germany., Adler T; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Prehn C; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Hans W; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Rozman J; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany., Becker L; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Aguilar-Pimentel JA; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Puk O; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany., Moreth K; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Dopatka M; Department of Experimental Neurology, Charite, Berlin, Germany., Walther DJ; Max Planck Institute for Molecular Genetics, Berlin, Germany., von Bohlen Und Halbach V; Institute of Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany., Rath M; Department of Human Genetics, University Medicine Greifswald, Greifswald, Germany; Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany., Delatycki M; Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Victoria, Australia., Bert B; Institute for Pharmacology and Toxicology, FB Veterinary Medicine, Free University, Berlin, Germany., Fink H; Institute for Pharmacology and Toxicology, FB Veterinary Medicine, Free University, Berlin, Germany., Blümlein K; Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany., Ralser M; Molecular Biology of Metabolism Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK., Van Dijck A; University of Antwerp, Department of Neurology - Antwerp University Hospital, Edegem, Belgium; Department of Medical Genetics, University of Antwerp, Antwerp, Belgium., Kooy F; University of Antwerp, Department of Neurology - Antwerp University Hospital, Edegem, Belgium., Stark Z; Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Victoria, Australia., Müller S; Institute of Biochemistry, University Greifswald, Greifswald, Germany., Scherthan H; Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich, Germany., Gecz J; School of Medicine, Robinson Research Institute, University of Adelaide, Adelaide, SA 5000, Australia; South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia., Wurst W; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; Technische Universität München, Freising-Weihenstephan, Germany; Deutsches Institut für Neurodegenerative Erkrankungen (DZNE), Site Munich, 80336 München, Germany; Munich Cluster for Systems Neurology (SyNergy), Adolf-Butenandt-Institut, Ludwig-Maximilians-Universität München, Schillerstr. 44, 80336 München, Germany., Wolf E; Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-University München, Feodor-Lynen Str. 25, 81377 München, Germany., Zimmer A; Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, Sigmund Freud Str. 25, 53127 Bonn, Germany., Klingenspor M; Technical University Munich, EKFZ - Else Kröner Fresenius Center for Nutritional Medicine, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany; ZIEL - Institute for Food and Health, Technical University Munich, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany., Graw J; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany., Klopstock T; Deutsches Institut für Neurodegenerative Erkrankungen (DZNE), Site Munich, 80336 München, Germany; Munich Cluster for Systems Neurology (SyNergy), Adolf-Butenandt-Institut, Ludwig-Maximilians-Universität München, Schillerstr. 44, 80336 München, Germany; Department of Neurology, Friedrich-Baur-Institute, Klinikum der Ludwig-Maximilians-Universität München, Ziemssenstr. 1a, 80336 München, Germany., Busch D; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Trogerstrasse 30, 81675 Munich, Germany., Adamski J; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; School of Life Science Weihenstephan, Technische Universität München, Alte Akademie 8, 85354 Freising, Germany., Fuchs H; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Gailus-Durner V; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., de Angelis MH; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany; School of Life Science Weihenstephan, Technische Universität München, Alte Akademie 8, 85354 Freising, Germany., von Bohlen Und Halbach O; Institute of Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany., Ropers HH; Max Planck Institute for Molecular Genetics, Berlin, Germany., Kuss AW; Department of Functional Genomics, Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Felix-Hausdorff-Strasse 8, 17489 Greifswald, Germany.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2019 Sep 01; Vol. 1865 (9), pp. 2083-2093. Date of Electronic Publication: 2018 Dec 14.
DOI: 10.1016/j.bbadis.2018.12.011
Abstrakt: Mutations in the X chromosomal tRNA 2'‑O‑methyltransferase FTSJ1 cause intellectual disability (ID). Although the gene is ubiquitously expressed affected individuals present no consistent clinical features beyond ID. In order to study the pathological mechanism involved in the aetiology of FTSJ1 deficiency-related cognitive impairment, we generated and characterized an Ftsj1 deficient mouse line based on the gene trapped stem cell line RRD143. Apart from an impaired learning capacity these mice presented with several statistically significantly altered features related to behaviour, pain sensing, bone and energy metabolism, the immune and the hormone system as well as gene expression. These findings show that Ftsj1 deficiency in mammals is not phenotypically restricted to the brain but affects various organ systems. Re-examination of ID patients with FTSJ1 mutations from two previously reported families showed that several features observed in the mouse model were recapitulated in some of the patients. Though the clinical spectrum related to Ftsj1 deficiency in mouse and man is variable, we suggest that an increased pain threshold may be more common in patients with FTSJ1 deficiency. Our findings demonstrate novel roles for Ftsj1 in maintaining proper cellular and tissue functions in a mammalian organism.
(Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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