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

Significance A novel version of the glutamate dehydrogenase gene, GLUD2 , evolved in the common ancestors of humans and apes. Based on sequence and expression pattern, GLUD2 has been suggested to play a role in glutamate metabolism in human and ape brains. We have generated transgenic mice carrying a human GLUD2 gene. Analysis of transcriptome and metabolome changes induced by GLUD2 in the cerebral cortex revealed no changes in glutamate concentration but instead changes to metabolic pathways centering on the TCA cycle during early postnatal development. These changes mirrored differences seen between human and macaque during cortex development, suggesting that GLUD2 may play a role during brain development in apes and humans, possibly by providing precursors for the biosynthesis of lipids.