Project description:We performed a comparative immunology case study of client-owned dogs to determine if immune and skin gene expression profiles in spontaneous canine pemphigus mirror those observed in human pemphigus
Project description:Total RNA from lymphocytes derived from skin lesions of three pemphigus patients and three healthy control subjects was used for this study. Elevated mRNA expression levels of the immune cells activation and chemotaxis were observed in pemphigus lesions.
Project description:Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to understand health and disease in the dog using investigative techniques including gene expression profiling. Accordingly, we now present a publicly accessible canine normal tissue gene expression database that will streamline the study of canine tissues and facilitate comparative genomic analysis with other mammals. The Affymetrix platform was utilized to catalogue the genetic signatures of normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. Public access and use of this data, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional cross-species comparisons. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. It is expected that this dataset will contribute to more advanced study of disease in the dog and biologically robust biomedical studies that utilize the dog as a model for translational research.
Project description:We performed targeted transcriptomic analysis on archival biopsies from client-owned dogs to examine immune and skin gene expression profiles in spontaneous canine epitheliotropic lymphoma (EL).
Project description:We performed targeted transcriptomic analysis on archival biopsies from client-owned dogs to examine immune and skin gene expression profiles in spontaneous canine epitheliotropic lymphoma (EL).
Project description:Canine pemphigus foliaceus (PF) is considered the most common autoimmune skin disease in dogs; the mechanism of PF disease development is currently poorly understood. Therefore, this study aimed to characterize the molecular mechanisms and altered biological pathways in the skin lesions of canine PF patients. Using an RNA microarray on formalin-fixed, paraffin-embedded samples, we analyzed the transcriptome of canine PF lesional skin (n = 7) compared to healthy skin (n = 5). Of the 800 genes analyzed, 420 differentially expressed genes (DEGs) (p < 0.05) were found. Of those, 338 genes were significantly upregulated, including pro-inflammatory and Th17-related genes. Cell type profiling found enhancement of several cell types, such as neutrophils, T-cells, and macrophages, in PF skin compared to healthy skin. Enrichment analyses of the upregulated DEGs resulted in 78 statistically significant process networks (FDR < 0.05), including the Janus kinase signal transducer and activator of transcription (JAK-STAT) and mitogen-activated protein kinase (MAPK) signaling. In conclusion, canine PF lesional immune signature resembles previously published changes in human pemphigus skin lesions. Further studies with canine PF lesional skin using next-generation sequencing (e.g., RNA sequencing, spatial transcriptomics, etc.) and the development of canine keratinocyte/skin explant PF models are needed to elucidate the pathogenesis of this debilitating disease.