INTRODUCTION AND OBJECTIVE: Obstruction and other processes that lead to renal damage can have different effects in adult versus developing kidneys. These differences are important for understanding pathophysiology, but also could influence selection of biomarkers used for detection of renal damage that could be used to guide intervention. In mice, significant renal development occurs postnatally, providing a model for understanding kidney development. To date, gene expression changes that occur mouse kidney growth and development postnatally have been poorly characterized. We describe here a comprehensive gene expression of the developing mouse kidney based on microarray profiling.
METHODS: C57BL/6 mice were sacrificed and kidneys were harvested at embryonic day E19.5, and postnatal days P1, P3, P5, P7, P10, P14, P21, P28 and P35. RNA was extracted from kidneys and transcript profiling was performed using Agilent microarrays. Transcripts that undergo abrupt transitions in expression level over the time course were identified using StepMiner analysis (Sahoo, 2007). Ingenuity pathway analysis (IPA) was used to analyze the biological function and gene networks of gene expression data.
RESULTS: Transcript levels for 13645 probes (representing 12769 genes) were modulated significantly over the time course, with 6949 up-regulated and 6696 down-regulated. IPA was used to identify genetic pathways, networks and functions significantly altered over the time course. Interestingly, in days P10 to P14 gene functions significantly altered were up-regulated exclusively with the functions represented including lipid metabolism, small molecule biochemistry and molecular transport. Between days P5 to P7 down-regulated genes predominated with enriched functions including, gene expression, cell cycle, protein synthesis and embryonic development. For P14 to P21 enriched functions included DNA replication, recombination and repair, cell cycle, tissue development, cellular assembly and organization, protein trafficking and cell morphology. In the late stages (P21 to P28) functional enrichment was seen for cell-to-cell signaling, tissue development, cellular movement.
CONCLUSIONS: This study provides the most comprehensive temporal survey of postnatal kidney development to date. This data set provides a framework for interpreting nephropathies, such as those induced by congenital obstruction.
Overall design: time series design
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