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Yuefang Zhou, Bendi Gong, Henry J. Kaminski; Genomic Profiling Reveals Pitx2 Controls Expression of Mature Extraocular Muscle Contraction–Related Genes. Invest. Ophthalmol. Vis. Sci. 2012;53(4):1821-1829. doi: https://doi.org/10.1167/iovs.12-9481.
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© ARVO (1962-2015); The Authors (2016-present)
To assess the influence of the Pitx2 transcription factor on the global gene expression profile of extraocular muscle (EOM) of mice.
Mice with a conditional knockout of Pitx2, designated Pitx2Δflox/Δflox and their control littermates Pitx2flox/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.
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.
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.
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