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

Molecular Autism

Brief Report

Baiba Svalbe¹  Solveiga Grinberga¹  Liga Zvejniece¹  Gundega Stelfa²  Edgars Liepinsh³  Maija Dambrova³  Helgi B. Schiöth⁴ 

[1]Latvian Institute of Organic Synthesis, Riga, Latvia

[2]Latvian Institute of Organic Synthesis, Riga, Latvia

[3]Latvia University of Life Sciences and Technologies, Jelgava, Latvia

[4]Latvian Institute of Organic Synthesis, Riga, Latvia

[5]Riga Stradins University, Riga, Latvia

[6]Uppsala University, Uppsala, Sweden

关键词: N6-trimethyllysine dioxygenase (TMLD);    Autism spectrum disorder;    Mice;    Gamma-butyrobetaine;    Mitochondria;   

DOI  :  10.1186/s13229-023-00560-7

 received in 2023-03-20, accepted in 2023-07-12,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

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