Abstract: Copy number variants (CNVs) of the chromosomal locus 16p11.2 has been predisposed individuals to neurodevelopmental diseases, including autism spectrum disorder, intellectual disability, epilepsy/seizures, dysmorphic features, congenital anomalies, macrocephaly, and microcephaly. Intracortical myelin is thought to play a significant role in the development of neural circuits and functional networks, with consistent evidence of typical network connectivity in children with neurodevelopmental disorders. Emerging imaging studies suggest abnormal white matter microstructure which can explain some of the associated clinical phenotypes including cognitive decline and developmental delay. In this study, we seek to discover myelin-related alternations in the corpus callosum using 16p11.2 alternation mouse model. We found, compared with controls, the myelin expression level alternation in the 16p11.2 duplication and deletion mouse model and these myelin changes will not improve with the mouse ageing. We further identified the cell number of mature and immature oligodendrocytes. We found the cell number was not changed in 16p11.2 CNVs mouse model. However, the myelin thickness changed in the area of the corpus callosum. These findings suggest that the myelin microstructure change is associated with the alternation of the 16p11.2 locus which may be the reason for neurodevelopmental disorders caused by 16p11.2 CNVs.
