Abstract
Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infection and increased incidence of autoimmune disorders and malignancy. WAS is caused by mutations in the was gene, which is expressed exclusively in hematopoietic cells; the spleen serves an important role in hematopoiesis and red blood cell clearance. However, to the best of our knowledge, detailed comparative analysis of the spleen between WASp-knockout (WAS-KO) and wild-type (WT) mice, particularly at the transcriptomic level, have not been reported. The present study investigated the differences in the transcriptomes of spleen tissue of 10-week-old WAS-KO mice. Comparison of the gene expression profiles of WAS-KO and WT mice revealed 1,964 differentially expressed genes (DEGs). Among these genes, 996 DEGs were upregulated and 968 were downregulated in WAS-KO mice. To determine the functions of DEGs, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed for significantly upregulated and downregulated DEGs. The results showed that the levels of cell senescence and apoptosis-associated genes were increased, antigen processing and presentation mechanisms involved in the immune response were damaged and signal transduction processes were impaired in the spleen of WAS-KO mice. Thus, was gene deletion may lead to anemia and hemolysis-associated disease, primarily due to increased osmotic fragility of red blood cells, low hemoglobin and increased bilirubin levels and serum ferritin. These results indicated that senescence and apoptosis of blood cells also play an important role in the occurrence of WAS. Therefore, the present findings provide a theoretical basis for further study to improve the treatment of WAS.