Pluto Bioinformatics

GSE80122: Mice carrying a human GLUD2 gene recapitulate aspects of human transcriptome and metabolome development

Bulk RNA sequencing

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 human genomic region containing the 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 affected predominantly genes involved in neuronal development. 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 stimulating lipid biosynthesis. SOURCE: Philipp Khaitovich (khaitovich@eva.mpg.de) - CAS-MPG Partner Institute for Computational Biology