Characterization of Social and Repetitive Behaviors ofMllt11/Af1q/TcF7cConditional Knockout Mice

Abstract

Mllt11(myeloid/lymphoid or mixed-lineage leukemia translocated to chromosome 11; also known asAf1q/TcF7c) has been identified as a novel regulator of neural development, playing a role in the migration and outgrowth of cortical projection neurons. We previously reported that the conditional inactivation of theMllt11gene in the mouse superficial cortex resulted in reduced connectivity of the corpus callosum and white fiber tracts, resulting in reduced cortical thickness. However, the behavioral consequences ofMllt11loss are unknown. Callosal abnormalities are thought to be present in 3-5% of all neurodevelopmental disorders and reduced corpus callosum volume correlates with core symptoms of autism spectrum disorder (ASD) in humans. Cortical thickness dysregulation is likewise shared among various neurodevelopmental disorders including ASD. We therefore investigated the behavioral consequences of conditional knockout ofMllt11in upper cortical layer 2/3 projection neurons using transgenicCux2iresCremice. Utilizing tasks designed to reflect core ASD symptoms, we examined the behaviors of both male and female conditional knockout animals. These tests included olfaction habituation/dishabituation, three-chambered social approach, marble burying, and nestlet shredding. We found sex-dependent disruptions in social preference, and nestlet shredding in animals lackingMllt11, with the female mice presenting with more disruptions than the males. Understanding the behavioral phenotype associated with genes of interest specifically in the context of sex differences is crucial to individualized treatment for neurodevelopmental disorders.