Research Of Novel Gene GLUD2 And Early Embryo Development

The emergence of novel genes accompanied with evolution of homo sapiens. Among the youngest genes of hominoid is GLUD2 (glutamate dehydrogenase 2) which appeared about 23 million years ago by retrotransposition from a housekeeping homolog GLUD1. The glutamate dehydrogenase catalyzes the reversible oxidative deamination of glutamate to a-ketoglutarate. a-ketoglutarate is an important component in tricarboxylic acid cycle. It not only participates both substantial and energetic regulation of the organism, but also act as a cofactor combining over 60 kinds of oxygenases. Their roles include collagen biosynthesis, DNA repair, RNA and chromatin modifications, fatty acid metabolism, and hypoxic sensing. Although the roles of a-ketoglutarate has been well studied in metabolism, the relationship of a-ketoglutarate and early embryo development is still largely unknown.To further investigate the influence on humans by acquisition of GLUD2, we generated GLUD2 transgenic mice. Despite of the similar metabolic rate compared to wild types, the transgenic mice displayed significant growth retardation. By HPLC-MS analysis, we revealed that while the a-ketoglutarate level of transgenic mice turned up, there was a slight decrease of glutamate level. Through investigation of serum components, we observed increases in uric acid and free fatty acid level and decreases in urea and creatine.Interestingly, according to statistics on quantities of offspring of GLUD2 transgenic mice, we found that the transmission ratio of GLUD2 gene distorted from the normal 1:1 value from male-transgenic mice, which means there were less transgenic mice than non-transgenicmice. Further research showed that the phenomenon of transmission ratio distortion had already appeared on E18.5. However, the morphology of testis of transgenic mice did not differ from that of non-transgenic. The transgenic mice neither produced distinguished sperms related to their genotypes. We then used in vitro fertilization technology to generate zygotes of GLUD2 and WT mice, and cultured the embryos till the developmental stage of blastocyst. By genotyping of the E3.5 embryos we found that transgenic blastocysts may be prone to apoptosis (still need be confirmed), thus indicating that GLUD2 gene may affect blastocyct development that lead to the decrease of amounts of transgenic embryos.In summary, our research defined GLUD2 as a distorter gene which may influence embryonic development. The substantial mechanism still remains unclear.