ABSTRACT: Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and increased incidence of autoimmune disorders and malignancies. WAS is caused by mutations in the was gene, which is expressed exclusively in hematopoietic cells, and the spleen plays an important role in hematopoiesis and red blood cell clearance. However, to date, detailed comparative analyses of the spleen between WASp-deficient (WAS-KO) mice and WT mice, particularly at the transcriptomic level, have not been reported. Here, we investigated the differences in the transcriptomes of spleen tissues of 10-week-old WAS-KO mice. Comparison of the gene expression profiles of WAS-KO and WT mice revealed 1964 differentially expressed genes (DEGs). Among these genes, 996 DEGs were upregulated, and 968 were downregulated in WAS-KO mice. To determine the functions of the DEGs, GO and KEGG enrichment analyses were performed for significantly upregulated and downregulated DEGs, respectively. The results showed that the levels of cell senescence and apoptosis-related genes were increased, that the antigen processing and presentation mechanisms involved in the immune response were damaged, and that signal transduction processes were impaired in the spleens of WAS-KO mice. Thus, was gene deletion may lead to anemia and hemolysis-related disease, mainly due to increased osmotic fragility of red blood cells, low hemoglobin, increased bilirubin levels and increased serum ferritin. These results indicate that senescence and apoptosis of blood cells also play an important role in the occurrence of WAS. However, most studies have focused only on the immune response. Therefore, the interesting findings of this paper can provide a stronger theoretical basis for further study and help improve the treatment of WAS. We performed gene expression profiling analysis using data obtained from RNA-seq of 2 different group of WT and WAS-KO mice.
