Ablation Of Microrna-155 And Neuroinflammation In A Mouse Model Of Cln1-Disease

Infantile neuronal ceroid lipofuscinosis (INCL), also known as CLN1-disease, is a devastating neurodegenerative lysosomal storage disorder (LSD), caused by inactivating mutations in the CLN1 gene. The Cln1(-/-) mice, which mimic INCL, manifest progressive neuroinflammation contributing to neurodegeneration. However, the underlying mechanism of neuroinflammation in INCL and in Cln1(-/-) mice has remained elusive. Previously, it has been reported that microRNA-155 (miR-155) regulates inflammation and miR profiling in Cln1(-/-) mouse brain showed that the level of miR-155 was upregulated. Thus, we sought to determine whether ablation of miR-155 in Cln1(-/-) mice may suppress neuroinflammation in these mice. Towards this goal, we generated Cln1(-/-)/miR-155(-/-) double-knockout mice and evaluated the inflammatory signatures in the brain. We found that the brains of double-KO mice manifest progressive neuroinflammatory changes virtually identical to those found in Cln1(-/-) mice. We conclude that ablation of miR-155 in Cln1(-/-) mice does not alter the neuroinflammatory trajectory in INCL mouse model. Published by Elsevier Inc.