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

First Author  Li Q Year  2016
Journal  Proc Natl Acad Sci U S A Volume  113
Issue  19 Pages  5358-63
PubMed ID  27118840 Mgi Jnum  J:232191
Mgi Id  MGI:5776300 Doi  10.1073/pnas.1519261113
Citation  Li Q, et al. (2016) Mice carrying a human GLUD2 gene recapitulate aspects of human transcriptome and metabolome development. Proc Natl Acad Sci U S A 113(19):5358-63
abstractText  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.
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