Summary: | 博士 === 國立陽明大學 === 生命科學暨基因體科學研究所 === 97 === Homeobox genes play important roles in developmental processes. Obox, oocytes specific homeobox gene, is a recently identified family of homeobox genes preferentially expressed in mouse oocytes. In our studies, we have identified 7 additional Obox gene copies at the A2 region on the mice chromosome 7. We predict that there are a cluster of 13 Obox related genes and spanning approximately 1.2 Mb at this genomic location. Most of Obox genes are expressed in mouse oocytes as maternal inherited components and decrease significantly in further development. By RT-PCR and whole-mount immunocytochemistry analysis, Obox genes are thought to be related to early embryo development. In support of this, siRNA knockdown of Obox genes in mouse early embryos reduced the developmental rate of embryos to develop to blastocyst stage. Uniquely among family members, we found Obox6 is expressed exclusively in early embryonic stages and exhibits an elevated expression from the 2-cell stage to the morula stage. To study the function of Obox6 in early embryogenesis, we generated Obox6 mutant mice using a gene targeting strategy. Obox6 mutant mice with genetic background of C57BL/6J inbred were born according to Mendelian rules without apparent defects. The mutant mice grew without morphological abnormalities and with normal fertility. The lack of an obvious phenotype in Obox6-null mice and altered RNA levels of some Obox genes raise the possibility that other members of the Obox gene family can compensate for Obox6 function during embryogenesis. However, knockout of Obox6 significantly reduced the developmental rate of early embryos under in vitro condition. Downregulation of genes for stress response and cell cycle regulation were identified by microarray analysis, this means they could be involved in the developmental defects of Obox6-null embryos. In conclusion, the identification of this family of homeobox genes provides a window to understand the complex gene regulatory mechanisms in mouse early embryo development.
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