Journal
PHYSIOLOGICAL GENOMICS
Volume 34, Issue 1, Pages 9-21Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/physiolgenomics.00285.2007
Keywords
corn1; microarray; cornea; serum response factor
Categories
Funding
- NEI NIH HHS [R01 EY016108, R01 EY016108-04, P30 EY016665-03, P30 EY-016665, P30 EY016665, R01 EY016108-03, R01 EY-016108, R01 EY016108-02, R01 EY016108-01] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007133, T32 GM007133-33, T32 GM-07133] Funding Source: Medline
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Remodeling of the actin cytoskeleton through actin dynamics (assembly and disassembly of filamentous actin) is known to be essential for numerous basic biological processes. In addition, recent studies have provided evidence that actin dynamics participate in the control of gene expression. A spontaneous mouse mutant, corneal disease 1 (corn1), is deficient for a regulator of actin dynamics, destrin (DSTN, also known as ADF), which causes epithelial hyperproliferation and neovascularization in the cornea. Dstn(corn1) mice exhibit an actin dynamics defect in the corneal epithelial cells, offering an in vivo model to investigate cellular mechanisms affected by the Dstn mutation and resultant actin dynamics abnormalities. To examine the effect of the Dstn(corn1) mutation on the gene expression profile, we performed a microarray analysis using the cornea from Dstn(corn1) and wild-type mice. A dramatic alteration of the gene expression profile was observed in the Dstn(corn1) cornea, with 1,226 annotated genes differentially expressed. Functional annotation of these genes revealed that the most significantly enriched functional categories are associated with actin and/or cytoskeleton. Among genes that belong to these categories, a considerable number of serum response factor target genes were found, indicating the possible existence of an actin-SRF pathway of transcriptional regulation in vivo. A comparative study using an allelic mutant strain with milder corneal phenotypes suggested that the level of filamentous actin may correlate with the level of gene expression changes. Our study shows that Dstn mutations and resultant actin dynamics abnormalities have a strong impact on the gene expression profile in vivo.
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