TY  - JOUR
AU  - Jensen, Lars R
AU  - Garrett, Lillian
AU  - Hölter, Sabine M
AU  - Rathkolb, Birgit
AU  - Rácz, Ildikó
AU  - Adler, Thure
AU  - Prehn, Cornelia
AU  - Hans, Wolfgang
AU  - Rozman, Jan
AU  - Becker, Lore
AU  - Aguilar-Pimentel, Juan Antonio
AU  - Puk, Oliver
AU  - Moreth, Kristin
AU  - Dopatka, Monika
AU  - Walther, Diego J
AU  - von Bohlen Und Halbach, Viola
AU  - Rath, Matthias
AU  - Delatycki, Martin
AU  - Bert, Bettina
AU  - Fink, Heidrun
AU  - Blümlein, Katharina
AU  - Ralser, Markus
AU  - Van Dijck, Anke
AU  - Kooy, Frank
AU  - Stark, Zornitza
AU  - Müller, Sabine
AU  - Scherthan, Harry
AU  - Gecz, Jozef
AU  - Wurst, Wolfgang
AU  - Wolf, Eckhard
AU  - Zimmer, Andreas
AU  - Klingenspor, Martin
AU  - Graw, Jochen
AU  - Klopstock, Thomas
AU  - Busch, Dirk
AU  - Adamski, Jerzy
AU  - Fuchs, Helmut
AU  - Gailus-Durner, Valérie
AU  - de Angelis, Martin Hrabě
AU  - von Bohlen Und Halbach, Oliver
AU  - Ropers, Hans-Hilger
AU  - Kuss, Andreas W
TI  - A mouse model for intellectual disability caused by mutations in the X-linked 2'‑O‑methyltransferase Ftsj1 gene.
JO  - Biochimica et biophysica acta / Molecular basis of disease
VL  - 1865
IS  - 9
SN  - 0925-4439
CY  - Amsterdam
PB  - Elsevier
M1  - DZNE-2020-07158
SP  - 2083-2093
PY  - 2019
AB  - 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.
KW  - Animals
KW  - Behavior, Animal
KW  - Cognition Disorders: etiology
KW  - Cognition Disorders: pathology
KW  - Disease Models, Animal
KW  - Family
KW  - Female
KW  - Intellectual Disability: etiology
KW  - Intellectual Disability: pathology
KW  - Male
KW  - Mental Retardation, X-Linked: genetics
KW  - Methyltransferases: genetics
KW  - Methyltransferases: metabolism
KW  - Methyltransferases: physiology
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - Mutation
KW  - Nociceptive Pain: etiology
KW  - Nociceptive Pain: pathology
KW  - Nuclear Proteins: genetics
KW  - Nuclear Proteins: metabolism
KW  - tRNA Methyltransferases: genetics
KW  - tRNA Methyltransferases: metabolism
KW  - tRNA Methyltransferases: physiology
LB  - PUB:(DE-HGF)16
C6  - pmid:30557699
DO  - DOI:10.1016/j.bbadis.2018.12.011
UR  - https://pub.dzne.de/record/140836
ER  -