Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1865, Issue 9, Pages 2083-2093Publisher
ELSEVIER
DOI: 10.1016/j.bbadis.2018.12.011
Keywords
Ftsj1; tRNA methyltransferase; Intellectual disability; X-linked; Mouse model
Funding
- German Federal Ministry of Education and Research [01KX1012]
- Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders) under e:Med Programme [01ZX1314H]
- German Science Foundation Collaborative Research Centre (CRC) 870
- Helmholtz Portfolio Theme 'Supercomputing and Modelling for the Human Brain' (SMHB)
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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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