Mouse models of 17q21.31 microdeletion and microduplication syndromes highlight the importance of Kansl1 for cognition

• DOI: 10.1371/journal.pgen.1006886
• Publication Date: 2017-07-13T17:29:25Z
• Authors: Thomas Arbogast; Giovanni Iacono; Claire Chevalier; Nurudeen O. Afinowi; Xander Houbaert; Matthijs C. van Eede; Christine Laliberte; Marie-Christine B...; Katrin Linda; Hamid Meziane; Mohammed Selloum; Tania Sorg; Nael Nadif Kasri; David A. Koolen; Henk G. Stunnenberg; R. Mark Henkelman; Maksym Kopanitsa; Yann Humeau; Bert B. A. De Vries; Yann Herault
• Keywords: dup

Koolen-de Vries syndrome (KdVS) is a multi-system disorder characterized by intellectual disability, friendly behavior, and congenital malformations. The caused either microdeletions in the 17q21.31 chromosomal region or variants KANSL1 gene. reciprocal microduplication associated with psychomotor delay, reduced social interaction. To investigate pathophysiology of microdeletion syndromes, we generated three mouse models: 1) deletion (Del/+); 2) duplication (Dup/+) syntenic region; 3) heterozygous Kansl1 (Kans1+/-) model. We found altered weight, general activity, behaviors, object recognition, fear conditioning memory craniofacial brain structural changes observed both Del/+ Dup/+ animals. By investigating hippocampus function, showed synaptic transmission defects mice. Mutant mice loss-of-function mutation displayed similar behavioral anatomical phenotypes compared to exception sociability phenotypes. Genes controlling chromatin organization, neurogenesis were upregulated Kansl1+/- Our results demonstrate implication manifestation KdVS extend substantially our knowledge about biological processes affected these mutations. Clear differences behavior gene expression profiles between suggested potential roles other genes deletion. Together, novel models provide new genetic tools valuable for development therapeutic approaches.