Mbnl2 loss alters novel context processing and impairs object recognition memory

Myotonic dystrophy type I (DM1) patients demonstrate visuospatial dysfunction and impaired performance in tasks requiring recognition or memory of figures and objects. In DM1, CUG expansion RNAs inactivate the Muscleblind-like (MBNL) proteins. We show that constitutive Mbnl2 inactivation in Mbnl2ΔE2/ΔE2 mice, selectively impairs object recognition memory in the novel object recognition test. When exploring the context of a novel arena in which the objects are later encountered, the Mbnl2ΔE2/ΔE2 dorsal hippocampus responds with a lack of enrichment for learning and memory related pathways, mounting instead transcriptome alterations predicted to impair growth and neuron viability. In Mbnl2ΔE2/ΔE2 mice, saturation effects may prevent deployment of a functionally relevant transcriptome response during novel context exploration. Post-novel context exploration alterations in genes implicated in tauopathy and dementia are observed in the Mbnl2ΔE2/ΔE2 dorsal hippocampus. Thus MBNL2 inactivation in DM1 patients may alter novel context processing in the dorsal hippocampus and impair object recognition memory. Comparative gene expression profiling analysis of RNA-seq data for the dorsal hippocampus in 129sv/C57BL/6j Mbnl2 WT and KO mice