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

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.

authors

Li Q,Guo S,Jiang X,Bryk J,Naumann R,Enard W,Tomita M,Sugimoto M,Khaitovich P,Pääbo S

doi

10.1073/pnas.1519261113

subject

Has Abstract

pub_date

2016-05-10 00:00:00

pages

5358-63

issue

19

eissn

0027-8424

issn

1091-6490

pii

1519261113

journal_volume

113

pub_type

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