Strain-specific modifier genes governing craniofacial phenotypes.

BACKGROUND:The presence of strain-specific modifier genes is known to modulate the phenotype and pathophysiology of mice harboring genetically engineered mutations. Thus, identification of genetic modifier genes is requisite to understanding control of phenotypic expression. c-Ski is a transcriptional regulator. Ski(-/-) mice on a C57BL6J (B6) background exhibit facial clefting, while Ski(-/-) mice on a 129P3 (129) background present with exencephaly. METHODS:In the present study, oligonucleotide-based gene expression profiling was used to identify potential strain-specific modifier gene candidates present in wild type mice of B6 and 129 genetic backgrounds. Changes in gene expression were verified by TaqMan quantitative real-time PCR. RESULTS:Steady-state levels of 89 genes demonstrated a significantly higher level of expression, and those of 68 genes demonstrated a significantly lower level of expression in the developing neural tubes from embryonic day (E) 8.5, B6 embryos when compared to expression levels in neural tubes derived from E 8.5, 129 embryos. CONCLUSIONS:Based on the results from the current comparative microarray study, and taking into consideration a number of relevant published reports, several potential strain-specific gene candidates, likely to modify the craniofacial phenotypes in various knockout mouse models have been identified.

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