Genomic profiling reveals Pitx2 controls expression of mature extraocular muscle contraction-related genes.
Genomic profiling reveals Pitx2 controls expression of mature extraocular muscle contraction-related genes.
复制标题
基因组分析揭示 Pitx2 控制成熟眼外肌收缩相关基因的表达。
DOI：
10.1167/iovs.12-9481
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发表时间：
2012
影响因子：
4.4
通讯作者：
Kaminski,HenryJ
中科院分区：
文献类型：
--
作者：
Zhou,Yuefang;Gong,Bendi;Kaminski,HenryJ
Purpose.: To assess the influence of the Pitx2 transcription factor on the global gene expression profile of extraocular muscle (EOM) of mice.Methods.: Mice with a conditional knockout of Pitx2, designated Pitx2 Δflox/Δflox and their control littermates Pitx2 flox/flox, were used. RNA was isolated from EOM obtained at 3, 6, and 12 weeks of age and processed for microarray-based profiling. Pairwise comparisons were performed between mice of the same age and differentially expressed gene lists were generated. Select genes from the profile were validated using real-time quantitative polymerase chain reaction and protein immunoblot. Ultrastructural analysis was performed to evaluate EOM sarcomeric structure.Results.: The number of differentially expressed genes was relatively small. Eleven upregulated and 23 downregulated transcripts were identified common to all three age groups in the Pitx2-deficient extraocular muscle compared with littermate controls. These fell into a range of categories including muscle-specific structural genes, transcription factors, and ion channels. The differentially expressed genes were primarily related to muscle contraction. We verified by protein and ultrastructural analysis that myomesin 2 was expressed in the Pitx2-deficient mice, and this was associated with development of M lines evident in their orbital region.Conclusions.: The global transcript expression analysis uncovered that Pitx2 primarily regulates a relatively select number of genes associated with muscle contraction. Pitx2 loss led to the development of M line structures, a feature more typical of other skeletal muscle.
