Neuroanatomical Phenotypes In The Reeler Mouse

Abstract The reeler mouse ( Reln ) has been proposed as a neurodevelopmental model for certain neurological and psychiatric conditions and has been studied by qualitative histochemistry and electron microscopy. Using magnetic resonance microscopy (MRM), we have quantitated for the first time the neuromorphology of Reln mice at a resolution of 21.5 μm. The neuroanatomical phenotypes of heterozygous and homozygous mutant Reln mice were compared to those of wild type (WT) littermates using morphometry and texture analysis. The cortical, hippocampal, and cerebellar phenotypes of the heterozygous and homozygous mutant Reln mice were confirmed, and new features were revealed. The Reln rl/rl mice possessed a smaller brain, and both Reln rl/+ and Reln rl/rl mice had increased ventricles compared to WT controls. Shape differences were found between WT and Reln rl/rl brains, specifically in cerebellum, olfactory bulbs, dorsomedial frontal and parietal cortex, certain regions of temporal and occipital lobes, as well as in the lateral ventricles and ventral hippocampus. These findings suggest that certain brain regions may be more severely impacted by the Reln mutation than others. Gadolinium-based active staining demonstrated that layers of the hippocampus were disorganized in Reln rl/rl mice and differences in thickness of these layers were identified between WT and Reln rl/rl mice. The intensity distributions characteristic to the dorsal, middle, and ventral hippocampus were altered in the Reln rl/rl , especially in the ventral hippocampus. These differences were quantified using skewness and modeling the intensity distributions with a Gaussian mixture. Our results suggest that structural features of Reln rl/rl brain most closely phenocopy those of patients with Norman–Roberts lissencephaly.