Analysis Of The Cutaneous Transcriptome And The Susceptibility To Listeria Monocytogenes In NIH Hairless Mice

Mice with spontaneous coat mutations are ideal animal models for studying skin development and tumorigenesis.In 2007,we found a mouse model with a spontaneous coat mutation(HL mice).In first part of 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.With spontaneous hair mutant mice is often used to study hair growth and hair follicle development.These mutant mice often exhibit immune dysfunctions.Listeria monocytogenes is an important food-borne bacterium.It has important applications in studying the immune response of animals to infection.In this experiment,we analysis the innate immunity of HL hairless mice(HL)and the impact of gut microbial polymorphisms by infected with L.monocytogenes(i.p.).Results show NIH hairless mice are susceptible than NIH mice to Listeria monocytogenes,including weight change,mortality,bacterial loads and histopathological lesions are more severe.The decrease of monocytes may be an important reason for these.The degree of spleen damage was relieved after co-housed,indicate the host guides gut microbial have worked in infection.High-throughput pyrosequencing of the 16 S rRNA demonstrated that the composition of the gut microbiota is different between NIH hairless and NIH mice.The infected with L.monocytogenes induced a trend of a large increase in Rikenellaceae and Gammaproteobacteria,and decrease in Clostridiales and Lachnospiraceae.Substantially reduce of Clostridiales in HL infected mice may cause a serious infection.Mycoplasma was only occur in NIH hairless mice and it is a biomarker of these.This improves our understanding of NIH hairless mice,for its use as a good animal model.