Please use this identifier to cite or link to this item:
10.1186/s13229-023-00560-7
Title: | Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels |
Authors: | Liepinsh, Edgars Svalbe, Baiba Stelfa, Gundega Grinberga, Solveiga Zvejniece, Liga Schiöth, Helgi B. Dambrova, Maija Rīga Stradiņš University |
Keywords: | Autism spectrum disorder;Gamma-butyrobetaine;Mice;Mitochondria;N6-trimethyllysine dioxygenase (TMLD);1.6 Biological sciences;3.1 Basic medicine;1.1. Scientific article indexed in Web of Science and/or Scopus database;Molecular Biology;Developmental Neuroscience;Developmental Biology;Psychiatry and Mental health;SDG 3 - Good Health and Well-being |
Issue Date: | 2023 |
Citation: | Liepinsh , E , Svalbe , B , Stelfa , G , Grinberga , S , Zvejniece , L , Schiöth , H B & Dambrova , M 2023 , ' Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels ' , Molecular Autism , vol. 14 , no. 1 , 29 . https://doi.org/10.1186/s13229-023-00560-7 |
Abstract: | Deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene was identified in probands with autism spectrum disorder (ASD). TMLHE encodes the first enzyme in carnitine biosynthesis, N6-trimethyllysine dioxygenase (TMLD). Researchers have suggested that carnitine depletion could be important for the development of ASD and cognitive, locomotor and social dysfunctions, but previous findings have been inconclusive regarding the specific role of endogenous carnitine. We developed a mouse knockout model with constitutive TMLD enzyme inactivation that exhibited a significant decrease in the carnitine by more than 90% compared to wild-type (WT) mice. However, we did not observe any significant social, cognitive, or repetitive-behavior changes associated with ASD in the knockout mice; muscle strength and coordination were also not affected. In addition, the life expectancy of knockout mice was similar to that of WT mice. In conclusion, knockout of Tmlh in mice does not induce an ASD phenotype or motor dysfunction despite extremely low carnitine and gamma-butyrobetaine concentrations. Moreover, inactivation of TMLD does not induce a phenotype similar to previously described primary carnitine deficiency; indeed, our results showed that low levels of carnitine sustained adequate energy production, muscle function and social behavior in mice. |
Description: | Funding Information: This research was supported by the Latvian Council of Science, project TRILYSOX (Grant No. LZP-2018/1-0082). The authors were supported by the European Union’s Horizon 2020 Research and Innovation Programme, Project FAT4BRAIN (Grant No. 857394). Publisher Copyright: © 2023, BioMed Central Ltd., part of Springer Nature. |
DOI: | 10.1186/s13229-023-00560-7 |
ISSN: | 2040-2392 |
Appears in Collections: | Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure |
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