Publication Database

A mouse model for intellectual disability caused by mutations in the X-linked 2'‑O‑methyltransferase Ftsj1 gene (2019)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Jensen, Lars R.

Garrett, Lillian

Hölter, Sabine M.

Rathkolb, Birgit

Rácz, Ildikó

Adler, Thure

Prehn, Cornelia

Hans, Wolfgang

Rozman, Jan

Becker, Lore

Aguilar-Pimentel, Juan Antonio

Puk, Oliver

Moreth, Kristin

Dopatka, Monika

Walther, Diego J.

von Bohlen Und Halbach, Viola

Rath, Matthias

Delatycki, Martin

Bert, Bettina

Fink, Heidrun (WE 14)

Blümlein, Katharina

Ralser, Markus

Van Dijck, Anke

Kooy, Frank

Stark, Zornitza

Müller, Sabine

Scherthan, Harry

Gecz, Jozef

Wurst, Wolfgang

Wolf, Eckhard

Zimmer, Andreas

Klingenspor, Martin

Graw, Jochen

Klopstock, Thomas

Busch, Dirk

Adamski, Jerzy

Fuchs, Helmut

Gailus-Durner, Valérie

de Angelis, Martin Hrabě

von Bohlen Und Halbach, Oliver

Ropers, Hans-Hilger

Kuss, Andreas W

Quelle

Biochimica et biophysica acta : BBA. Molecular basis of disease

Bandzählung: 1865

Heftzählung: 9

Seiten: 2083 – 2093

ISSN: 1879-260x

Sprache

Englisch

Verweise

URL (Volltext): https://www.sciencedirect.com/science/article/pii/S0925443918304976?via%3Dihub

DOI: 10.1016/j.bbadis.2018.12.011

Pubmed: 30557699

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.