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

Qian Li, Song Guo, Xi Jiang, Jaroslaw Bryk, Ronald Naumann, Wolfgang Enard, Masaru Tomita, Masahiro Sugimoto, Philipp Khaitovich, Svante Pääbo

    Research output: Contribution to journalArticlepeer-review

    20 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)5358-5363
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume113
    Issue number19
    DOIs
    Publication statusPublished - 10 May 2016

    Keywords

    • Brain metabolism
    • GLUD2
    • Human evolution

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