Research Paper Volume 9, Issue 3 pp 706—740

Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruption

Figure 2. Thymic structural dysregulation in GIT2KO mice. Significant age-dependent bodyweight variations observed between WT and GIT2KO mice (A). Thymic weight was reduced for all mice with increasing age (B) while only GIT2KO thymocytes, normalized to thymic weight, were reduced with age (C). Compared to age-matched 12 month old WT mice (left image panel) gross cortico-medullary thymic structure was disrupted in GIT2KO (right panel) mice (D: original magnification: 4x. Scale bar: 200 μm). Troma-I transcript expression is significantly reduced in GIT2KO thymus at 12 months of age compared to WT controls (E). WT and GIT2KO histogram data is indicated by black and lined bars respectively: mean ± SEM is indicated on each histogram. Months of age is abbreviated to m.o. *p<0.05, **p<0.01, ***p<0.001. Significantly-regulated (p<0.05) transcripts differentially expressed in GIT2KO versus WT thymus are indicated – specifically highlighted up- (red) or down-regulated transcripts are denoted by their official Gene Symbol (F). Ingenuity Pathway Analysis (IPA) Canonical Signaling Pathway analysis of transcripts differentially and significantly regulated (% of transcripts in pathway - upregulated in red, down-regulated in green are shown) between 12 month old GIT2KO and WT thymus (Top 10 enrichment probability pathways indicated: yellow line indicates pathway enrichment probability) (G). IPA BioFunction Z score activation analysis was performed on significantly-regulated differential transcripts from GIT2KO thymus compared to WT (Top 10 activation Z-score BioFunctions indicated) (H). Pathways/BioFunctions were only considered significantly populated with >2 transcripts at a p value of <0.05. Transcript arrays were performed in triplicate.