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.