A mouse model for intellectual disability caused by mutations in the X-linked 2'Omethyltransferase Ftsj1 gene

Autor: Andreas W. Kuss, Ildiko Racz, Lore Becker, Thomas Klopstock, Lillian Garrett, Lars R. Jensen, Markus Ralser, Jozef Gecz, Martin Hrabě de Angelis, Matthias Rath, Hans-Hilger Ropers, Martin Klingenspor, Eckhard Wolf, Juan Antonio Aguilar-Pimentel, Thure Adler, Wolfgang Wurst, Anke Van Dijck, Sabine Müller, Jan Rozman, Viola von Bohlen und Halbach, Andreas Zimmer, Kristin Moreth, Harry Scherthan, Katharina Blümlein, Martin B. Delatycki, Birgit Rathkolb, Diego J. Walther, Jochen Graw, R. Frank Kooy, Jerzy Adamski, Valerie Gailus-Durner, Oliver Puk, Helmut Fuchs, Sabine M. Hölter, Bettina Bert, Oliver von Bohlen und Halbach, Cornelia Prehn, Wolfgang Hans, Zornitza Stark, Monika Dopatka, Dirk H. Busch, Heidrun Fink
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
Methyltransferase
medicine.disease_cause
Nociceptive Pain
Mice
0302 clinical medicine
Ecology
Evolution & Ethology
Intellectual disability
Gene expression
Genetics
Mice
Knockout
Chemical Biology & High Throughput
0303 health sciences
Mutation
tRNA Methyltransferases
Behavior
Animal
Physics
Nuclear Proteins
genetics [Mental Retardation
X-Linked]
genetics [Nuclear Proteins]
genetics [tRNA Methyltransferases]
ddc
Chemistry
Molecular Medicine
Female
Synthetic Biology
etiology [Intellectual Disability]
metabolism [Nuclear Proteins]
pathology [Nociceptive Pain]
Biology
pathology [Intellectual Disability]
03 medical and health sciences
physiology [Methyltransferases]
Immune system
Intellectual Disability
medicine
Animals
metabolism [tRNA Methyltransferases]
Family
ddc:610
metabolism [Methyltransferases]
Molecular Biology
Gene
physiology [tRNA Methyltransferases]
030304 developmental biology
Computational & Systems Biology
TRNA Methyltransferase
etiology [Cognition Disorders]
Methyltransferases
medicine.disease
TRNA Methyltransferases
Mice
Inbred C57BL
Disease Models
Animal
Metabolism
etiology [Nociceptive Pain]
genetics [Methyltransferases]
Mental Retardation
X-Linked
pathology [Cognition Disorders]
Human medicine
Cognition Disorders
030217 neurology & neurosurgery
Zdroj: Biochim Biophys Acta Mol Basis Dis
Biochimica et biophysica acta : molecular basis of disease
Biochimica et biophysica acta / Molecular basis of disease 1865(9), 2083-2093 (2019). doi:10.1016/j.bbadis.2018.12.011
ISSN: 0925-4439
Popis: 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.
Databáze: OpenAIRE
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