Mice Carrying a Human GLUD2 Gene Recapitulate Aspects of Human Transcriptome and Metabolome Development

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2016 Apr 28

PMID 27118840

Citations 23

Authors

Qian Li

Song Guo

Xi Jiang

Jaroslaw Bryk

Ronald Naumann

Wolfgang Enard

Masaru Tomita

Masahiro Sugimoto

Philipp Khaitovich

Svante Paabo

Affiliations

Soon will be listed here.

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.

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