Loss of Schlafen3 influences the expression levels of Schlafen family members in ileum, thymus, and spleen tissue

Background: The Schlafen (Slfn) family proteins are important for regulation of cell growth, cell differentiation and cell cycle progression. We sought to distinguish Slfn family expression in Slfn3 knockout (KO) mice after RNA sequencing analysis of Slfn3KO vs. wildtype (WT) mice revealed varying expressions of Slfn family in ileal mucosa. Methods: Quantitative PCR analysis of Slfn members was evaluated in ileal mucosa, thymus and spleen tissue since Slfn family members have roles in differentiating intestinal and immune cells. Results: Ileal mucosa of Slfn3KO mice displayed a decrease in Slfn3, 4, 8 and 9 while Slfn1 and 5 increased in mRNA expression vs. WT mice. Thymic tissue had a Slfn9 increase and a Slfn4 decrease while splenic tissue had a Slfn8 and Slfn9 increase in Slfn3KO mice vs. WT mice. These differential expressions of Slfn members could indicate a feedback regulatory mechanism within the Slfn family. Indeed, MATCH() tool from geneXplain predicted that all Slfn members have regions in their promoters for the Kruppel-like factor-6 transcription factor. In addition, NFAT related factors, ING4, ZNF333 and KLF4 are also predicted to bind in up to 6 of the 8 Slfn promoters. This study further describes a possible autoregulatory mechanism amongst the Slfn family members which could be important in how they regulate the differentiation of various cell types.