Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels

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dc.contributor.authorLiepinsh, Edgars
dc.contributor.authorSvalbe, Baiba
dc.contributor.authorStelfa, Gundega
dc.contributor.authorGrinberga, Solveiga
dc.contributor.authorZvejniece, Liga
dc.contributor.authorSchiƶth, Helgi B.
dc.contributor.authorDambrova, Maija
dc.contributor.institutionRÄ«ga StradiņŔ University
dc.date.accessioned2023-08-22T09:45:02Z
dc.date.available2023-08-22T09:45:02Z
dc.date.issued2023
dc.descriptionFunding 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 Unionā€™s Horizon 2020 Research and Innovation Programme, Project FAT4BRAIN (Grant No. 857394). Publisher Copyright: Ā© 2023, BioMed Central Ltd., part of Springer Nature.
dc.description.abstractDeletion 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.en
dc.description.statusPeer reviewed
dc.format.extent890228
dc.identifier.citationLiepinsh, E, Svalbe, B, Stelfa, G, Grinberga, S, Zvejniece, L, Schiƶth, 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
dc.identifier.doi10.1186/s13229-023-00560-7
dc.identifier.issn2040-2392
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/14843
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85167371142&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofMolecular Autism
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectAutism spectrum disorder
dc.subjectGamma-butyrobetaine
dc.subjectMice
dc.subjectMitochondria
dc.subjectN6-trimethyllysine dioxygenase (TMLD)
dc.subject1.6 Biological sciences
dc.subject3.1 Basic medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectMolecular Biology
dc.subjectDevelopmental Neuroscience
dc.subjectDevelopmental Biology
dc.subjectPsychiatry and Mental health
dc.subjectSDG 3 - Good Health and Well-being
dc.titleKnockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levelsen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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