Mice carrying a human GLUD2 gene recapitulate aspects of human transcriptome and metabolome development

Li, Qian, Guo, Song, Jiang, Xi, Bryk, Jarek, Naumann, Ronald, Enard, Wolfgang, Tomita, Masaru, Sugimoto, Masahiro, Khaitovich, Philipp and Pääbo, Svante (2016) Mice carrying a human GLUD2 gene recapitulate aspects of human transcriptome and metabolome development. Proceedings of the National Academy of Sciences, 113 (19). pp. 5358-5363. ISSN 0027-8424

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Abstract

Whereas all mammals have one glutamate dehydrogenase gene (GLUD1), humans and apes carry an additional gene (GLUD2), which encodes an enzyme with distinct biochemical properties. We inserted a bacterial artificial chromosome containing the human GLUD2 gene into mice and analyzed the resulting changes in the transcriptome and metabolome during postnatal brain development. Effects were most pronounced early postnatally, and predominantly genes involved in neuronal development were affected. Remarkably, the effects in the transgenic mice partially parallel the transcriptome and metabolome differences seen between humans and macaques analyzed. Notably, the introduction of GLUD2 did not affect glutamate levels in mice, consistent with observations in the primates. Instead, the metabolic effects of GLUD2 center on the tricarboxylic acid cycle, suggesting that GLUD2 affects carbon flux during early brain development, possibly supporting lipid biosynthesis.

Item Type:	Article
Subjects:	Q Science > Q Science (General) Q Science > QH Natural history > QH301 Biology
Schools:	School of Applied Sciences
Related URLs:	Author
Depositing User:	Sharon Beastall
Date Deposited:	11 May 2016 11:19
Last Modified:	28 Aug 2021 17:10
URI:	http://eprints.hud.ac.uk/id/eprint/28345

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