Transgenic modeling of Ndr2 gene amplification reveals disturbance of hippocampus circuitry and function

• DOI: 10.1016/j.isci.2021.102868
• Publication Date: 2021-07-19T06:08:26Z
• Authors: Deniz A. Madencioglu; Gürsel Çalışkan; Pingan Yuanxiang; Kati Rehberg; Yunus E. Demiray; Emre Kul; Alexander Engler; Hussam Hayani; Jorge R. Bergado-...; Anne Kummer; Iris Müller; Inseon Song; Alexander Dityatev; Thilo Kähne; Michael R. Kreutz; Oliver Stork
• Keywords: Forebrain; Doublecortin

Duplications and deletions of short chromosomal fragments are increasingly recognized as the cause for rare neurodevelopmental conditions disorders. The NDR2 gene encodes a protein kinase important neuronal development is part microduplication region on chromosome 12 that associated with intellectual disabilities, autism, epilepsy. We developed conditional transgenic mouse increased Ndr2 expression in postmigratory forebrain neurons to study consequences an dosage this Hippo pathway brain circuitry cognitive functions. Our analysis reveals reduced terminal fields synaptic transmission hippocampal mossy fibers, altered network activity, deficits fiber-dependent behaviors. Reduced doublecortin interactome indicate disturbs maturation granule cells dentate gyrus. Together, our data suggest may critically contribute disabilities upon amplification.