Ablation of microRNA-155 and neuroinflammation in a mouse model of CLN1-disease

Abstract

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.