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.
journal_name
Proc Natl Acad Sci U S Aauthors
Li Q,Guo S,Jiang X,Bryk J,Naumann R,Enard W,Tomita M,Sugimoto M,Khaitovich P,Pääbo Sdoi
10.1073/pnas.1519261113subject
Has Abstractpub_date
2016-05-10 00:00:00pages
5358-63issue
19eissn
0027-8424issn
1091-6490pii
1519261113journal_volume
113pub_type
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