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

Lars R. Jensen, Lillian Garrett, Sabine M. Hölter, Birgit Rathkolb, Ildikó Rácz, T. Adler, Cornelia Prehn, Wolfgang Hans, Jan Rozman, Lore Becker, Juan Antonio Aguilar-Pimentel, Oliver Puk, Kristin Moreth, Monika Dopatka, Diego J. Walther, V. von Bohlen und Halbach, Matthias Rath, Martin Delatycki, Bettina Bert, Heidrun Fink & 22 others Katharina Blümlein, Markus Ralser, Anke Van Dijck, F. Kooy, Zornitza Stark, Sabine Müller, H. Scherthan, Jozef Gecz, Wolfgang Wurst, Eckhard Wolf, Andreas Zimmer, Martin Klingenspor, Jochen Graw, Thomas Klopstock, Dirk Busch, J. Adamski, Helmut Fuchs, Valérie Gailus-Durner, Martin Hrabě de Angelis, Oliver von Bohlen und Halbach, Hans Hilger Ropers, Andreas W. Kuss

Research output: Contribution to journalArticle

Abstract

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.

LanguageEnglish
Pages2083-2093
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1865
Issue number9
DOIs
Publication statusPublished - 1 Sep 2019

Keywords

  • Ftsj1
  • Intellectual disability
  • Mouse model
  • X-linked
  • tRNA methyltransferase

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

Jensen, Lars R. ; Garrett, Lillian ; Hölter, Sabine M. ; Rathkolb, Birgit ; Rácz, Ildikó ; Adler, T. ; 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, V. ; Rath, Matthias ; Delatycki, Martin ; Bert, Bettina ; Fink, Heidrun ; Blümlein, Katharina ; Ralser, Markus ; Van Dijck, Anke ; Kooy, F. ; Stark, Zornitza ; Müller, Sabine ; Scherthan, H. ; Gecz, Jozef ; Wurst, Wolfgang ; Wolf, Eckhard ; Zimmer, Andreas ; Klingenspor, Martin ; Graw, Jochen ; Klopstock, Thomas ; Busch, Dirk ; Adamski, J. ; Fuchs, Helmut ; Gailus-Durner, Valérie ; de Angelis, Martin Hrabě ; von Bohlen und Halbach, Oliver ; Ropers, Hans Hilger ; Kuss, Andreas W. / A mouse model for intellectual disability caused by mutations in the X-linked 2′‑O‑methyltransferase Ftsj1 gene. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2019 ; Vol. 1865, No. 9. pp. 2083-2093.
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title = "A mouse model for intellectual disability caused by mutations in the X-linked 2′‑O‑methyltransferase Ftsj1 gene",
abstract = "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.",
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Jensen, LR, Garrett, L, Hölter, SM, Rathkolb, B, Rácz, I, Adler, T, Prehn, C, Hans, W, Rozman, J, Becker, L, Aguilar-Pimentel, JA, Puk, O, Moreth, K, Dopatka, M, Walther, DJ, von Bohlen und Halbach, V, Rath, M, Delatycki, M, Bert, B, Fink, H, Blümlein, K, Ralser, M, Van Dijck, A, Kooy, F, Stark, Z, Müller, S, Scherthan, H, Gecz, J, Wurst, W, Wolf, E, Zimmer, A, Klingenspor, M, Graw, J, Klopstock, T, Busch, D, Adamski, J, Fuchs, H, Gailus-Durner, V, de Angelis, MH, von Bohlen und Halbach, O, Ropers, HH & Kuss, AW 2019, 'A mouse model for intellectual disability caused by mutations in the X-linked 2′‑O‑methyltransferase Ftsj1 gene', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1865, no. 9, pp. 2083-2093. https://doi.org/10.1016/j.bbadis.2018.12.011

A mouse model for intellectual disability caused by mutations in the X-linked 2′‑O‑methyltransferase Ftsj1 gene. / Jensen, Lars R.; Garrett, Lillian; Hölter, Sabine M.; Rathkolb, Birgit; Rácz, Ildikó; Adler, T.; 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, V.; Rath, Matthias; Delatycki, Martin; Bert, Bettina; Fink, Heidrun; Blümlein, Katharina; Ralser, Markus; Van Dijck, Anke; Kooy, F.; Stark, Zornitza; Müller, Sabine; Scherthan, H.; Gecz, Jozef; Wurst, Wolfgang; Wolf, Eckhard; Zimmer, Andreas; Klingenspor, Martin; Graw, Jochen; Klopstock, Thomas; Busch, Dirk; Adamski, J.; Fuchs, Helmut; Gailus-Durner, Valérie; de Angelis, Martin Hrabě; von Bohlen und Halbach, Oliver; Ropers, Hans Hilger; Kuss, Andreas W.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1865, No. 9, 01.09.2019, p. 2083-2093.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A mouse model for intellectual disability caused by mutations in the X-linked 2′‑O‑methyltransferase Ftsj1 gene

AU - Jensen, Lars R.

AU - Garrett, Lillian

AU - Hölter, Sabine M.

AU - Rathkolb, Birgit

AU - Rácz, Ildikó

AU - Adler, T.

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, V.

AU - Rath, Matthias

AU - Delatycki, Martin

AU - Bert, Bettina

AU - Fink, Heidrun

AU - Blümlein, Katharina

AU - Ralser, Markus

AU - Van Dijck, Anke

AU - Kooy, F.

AU - Stark, Zornitza

AU - Müller, Sabine

AU - Scherthan, H.

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, J.

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.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

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KW - Ftsj1

KW - Intellectual disability

KW - Mouse model

KW - X-linked

KW - tRNA methyltransferase

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U2 - 10.1016/j.bbadis.2018.12.011

DO - 10.1016/j.bbadis.2018.12.011

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VL - 1865

SP - 2083

EP - 2093

JO - Biochimica et Biophysica Acta - Molecular Basis of Disease

T2 - Biochimica et Biophysica Acta - Molecular Basis of Disease

JF - Biochimica et Biophysica Acta - Molecular Basis of Disease

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