Transcriptional profiling of PRKG2-null growth plate identifies putative down-stream targets of PRKG2

摘要: Kinase activity of cGMP-dependent, type II, protein kinase (PRKG2) is required for the proliferative to hypertrophic transition growth plate chondrocytes during endochondral ossification. Loss PRKG2 function in rodent and bovine models results dwarfism. The objective this study was identify pathways regulated or impacted by loss that may be responsible disproportionate dwarfism at molecular level. Microarray technology used compare cartilage gene expression dwarf versus unaffected Angus cattle putative downstream targets PRGK2. Pathway enrichment 1284 transcripts (nominal p < 0.05) candidate consistent with phenotype Analysis DAVID pathway suite identified differentially expressed genes clustered MHC, cytochrome B, WNT, Muc1 pathways. A second analysis studio software a host (e.g. CREB1, P21, CTNNB1, EGFR, EP300, JUN, P53, RHOA, SRC). As proof concept, we validated differential five including CEBPA, BRCA1, BUB1, CD58, VDR real-time PCR (p < 0.05). Known novel were as enriched study. This indicates P53 well additional increased proliferation apoptosis due achondroplastic