Novel finding: Mutation in the X-linked Ftsj1 gene caused not only intellectual disability in mice and men, but affects also additional organ systems

Source: GMC

Intellectual disability (ID) is a major developmental disorder and currently it was estimated to affect around 1% of the population at average. The disease is defined by significant limitations in intellectual performance and a reduction of conceptual, social and practical skills with an onset before the age of 18. Mutations in the mammalian X chromosomal tRNA 2’-O-methyltransferase FTSJ1 cause ID in humans. The function of the gene is largely uncharacterized and the consequences of FTSJ1 deficiency in humans seem to affect mainly cognition, although the gene is ubiquitously expressed.

In a joint project, scientists of the University of Greifswald together with colleagues of the German Mouse Clinic generated and analyzed a mouse model for ID caused by mutations in the X-linked Ftsj1 gene in order to investigate the disease and the function of the gene in more detail. ID was determined in the mouse model, but the mutant mice showed additional features that were not linked to Ftsj1 deficiency before. After re-examination of the patients, some of the new features were observed in their clinical presentation. This sheds new light on this disorder and gives first indications regarding the function of Ftsj1 in the mammalian organism. The study was published recently in BBA Molecular Basis of Disease.

In the systemic screening pipeline, the German Mouse Clinic examined all clinical relevant organ systems. In addition, mice were tested in specialized behavior tests as Y-maze and Intellicage. Apart from an impaired learning capacity especially in male mutants, that was comparable to ID, these mice presented significantly altered features related to behaviour, pain sensing, bone and energy metabolism, the immune and the hormone system as well gene expression. These findings showed that Ftsj1 deficiency in mammals might not be phenotypically restricted to the brain, but affects various organ systems. Based on the phenotypic features found in Ftsj1 deficient mice, the mutation carriers from two previously published families A003 and MRX9 were re-examined. The clinicians did observe individual alterations related to cholesterol levels, muscle strength, hypoalgesia, hematology, triglyceride and hormone levels in patients or the female carrier, which strongly suggest that the effects of FTSJ1 deficiency are not restricted to cognitive features in humans either. An increased pain threshold was found in the mutant mice, and in affected individuals from both investigated ID families. This could be a feature more common in patients with FTSJ1 deficiency, but too few ID families with FTSJ1 mutations have been identified yet to define a syndrome.


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.

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

Biochim Biophys Acta Mol Basis Dis. 2018 Dec 14. pii: S0925-4439(18)30497-6. doi: 10.1016/j.bbadis.2018.12.011. [Epub ahead of print]