10779/crick.11371434.v1
Lars R Jensen
Lars R
Jensen
Lillian Garrett
Lillian
Garrett
Sabine M Hölter
Sabine M
Hölter
Birgit Rathkolb
Birgit
Rathkolb
Ildikó Rácz
Ildikó
Rácz
Thure Adler
Thure
Adler
Cornelia Prehn
Cornelia
Prehn
Wolfgang Hans
Wolfgang
Hans
Jan Rozman
Jan
Rozman
Lore Becker
Lore
Becker
Juan Antonio Aguilar-Pimentel
Juan Antonio
Aguilar-Pimentel
Oliver Puk
Oliver
Puk
Kristin Moreth
Kristin
Moreth
Monika Dopatka
Monika
Dopatka
Diego J Walther
Diego J
Walther
Viola von Bohlen und Halbach
Viola
von Bohlen und Halbach
Matthias Rath
Matthias
Rath
Martin Delatycki
Martin
Delatycki
Bettina Bert
Bettina
Bert
Heidrun Fink
Heidrun
Fink
Katharina Blümlein
Katharina
Blümlein
Markus Ralser
Markus
Ralser
Anke Van Dijck
Anke
Van Dijck
Frank Kooy
Frank
Kooy
Zornitza Stark
Zornitza
Stark
Sabine Müller
Sabine
Müller
Harry Scherthan
Harry
Scherthan
Jozef Gecz
Jozef
Gecz
Wolfgang Wurst
Wolfgang
Wurst
Eckhard Wolf
Eckhard
Wolf
Andreas Zimmer
Andreas
Zimmer
Martin Klingenspor
Martin
Klingenspor
Jochen Graw
Jochen
Graw
Thomas Klopstock
Thomas
Klopstock
Dirk Busch
Dirk
Busch
Jerzy Adamski
Jerzy
Adamski
Helmut Fuchs
Helmut
Fuchs
Valérie Gailus-Durner
Valérie
Gailus-Durner
Martin Hrabĕ de Angelis
Martin Hrabĕ
de Angelis
Oliver von Bohlen und Halbach
Oliver
von Bohlen und Halbach
Hans-Hilger Ropers
Hans-Hilger
Ropers
Andreas W Kuss
Andreas W
Kuss
A mouse model for intellectual disability caused by mutations in the X-linked 2'-O-methyltransferase Ftsj1 gene
The Francis Crick Institute
2019
Ftsj1
Intellectual disability
Mouse model
X-linked
tRNA methyltransferase
Ralser FC001134
Biochemistry & Molecular Biology
0601 Biochemistry and Cell Biology
1101 Medical Biochemistry and Metabolomics
1103 Clinical Sciences
2019-12-16 17:42:55
Journal contribution
https://crick.figshare.com/articles/journal_contribution/A_mouse_model_for_intellectual_disability_caused_by_mutations_in_the_X-linked_2_-O-methyltransferase_Ftsj1_gene/11371434
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.