The predominant class of gene expression changes were in inflammatory genes, which increased in an age-dependent manner, coinciding with increases in tau phosphorylation, decreases in markers of neuronal activity, and behavioral deficits. These inflammatory genes formed a network highly reminiscent of the immune function gene expression network perturbed in AD. Laser microdissection of hippocampal subfields revealed additional gene expression changes in AD-relevant synaptic transmission pathways. These perturbations may contribute to the observed behavioral deficits. Overall these data suggest that the rTg4510 recapitulates several aspects of human neurodegenerative disease, and could be used as a reasonable preclinical model to test disease relevant hypotheses and evaluate candidate therapeutic interventions. We also describe our structure-based analysis of mutations that result in loss of the Uracil essential CdnL function and impair cell viability. These include mutations that disrupt the interaction with RNAP-b as well as those that leave this interaction intact. We present data that CdnL stabilizes open complex formation and stimulates transcription at an rRNA promoter by RNAP holoenzyme containing the major M. xanthus housekeeping sA, and that the loss-of-function CdnL mutants lack this activity. Our results are discussed in the context of our data of the RNAP recognition domain of TtCdnL, the T. Lamivudine thermophilus CdnL homolog and those from other groups on full-length TtCdnL and MtCdnL, both of which exist in bacteria lacking CarD as well as DksA. The involvement of CdnL in sA-dependent rRNA promoter activity and of CarD in the action of several ECF-s factors thus illustrates the evolution of two related members of an important bacterial protein family to regulate promoter activity dependent on different s factors. The CdnL NMR solution structure and its structure-based mutational analysis in this study provide molecular insights into the cellular roles and modes of action of this RNAP-binding protein that is essential for growth and viability but has unknown functions in M. xanthus. CdnL has a two-domain architecture in solution.