Cutaneous transcriptome analysis in NIH hairless mice

Mice with spontaneous coat mutations are ideal animal models for studying skin development and tumorigenesis. In this study, skin hair growth cycle abnormalities were examined in NIH hairless mice 42 days after birth (P42) by using hematoxylin-eosin (H&E) staining. To examine the gene expression patterns in the skin of mutant mice, the dorsal skin of P42 female NIH mice and NIH hairless mice was sequenced by RNA-Seq, and 5,068 differentially expressed genes (DEGs) were identified (false discovery rate [FDR] ≥ 2, P < 0.05). A pathway analysis showed that basal cell carcinoma, the cell cycle and the Hippo, Hedgehog and Wnt signaling pathways were up-regulated in NIH hairless mice. Previous studies have shown that these pathways are closely associated with cell proliferation, cell cycle, organ size and cancer development. In contrast, signal transduction, bacterial and parasitic infection, and receptor-mediated pathways, including calcium signaling, were down-regulated in NIH hairless mice. A gene interaction network analysis was performed to identify genes related to hair follicle development. To verify the reliability of the RNA-Seq results, we used q-PCR to analyze 12 key genes identified from the gene interaction network analysis, including eight down-regulated and four up-regulated genes, and the results confirmed the reliability of the RNA-Seq results. Finally, we constructed the differential gene expression profiles of mutant mice by RNA-Seq. NIH hairless mice exhibited abnormalities in hair development and immune-related pathways. Pik3r1 and Pik3r3 were identified as key genes, laying the foundation for additional in-depth studies of hairless mice.