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 m. 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.

Advances in behavioral genetics: mouse models of autism

“…9,155 In adult mice, Reelin protein is synthesized and secreted from GABAergic interneurons in cortex and hippocampus, with extracellular localization to dendrites and dendritic spines. 156 Loss of Reln function in mice leads to overt motor impairment, increased anxiety, learning deficits and abnormal neuroanatomy, [157][158][159][160] as well as aberrant striatal LTP. 159 As described previously, reeler mouse pups have markedly lower rates of ultrasonic vocalization, dependent on gender and history of maternal separation.…”

Evaluation of White Matter Changes in Agyria–Pachygyria Complex Using Diffusion Tensor Imaging

“…[39][40]43,44 Animal models of lissencephaly show widespread defects in the white matter, including disorganized and shortened axons, and disrupted axonal projections across the midline. 45,46 Because axonogenesis requires a reorganization of the growth cone and its microtubule-and actin-rich domains 47 and because genes implicated in lissencephaly act directly or indirectly on the microtubule-dynein cytoskeleton that promotes axonal outgrowth and maintains axonal stability, [48][49][50] it is not surprising that agyria-pachygyria patients have disrupted axonal projection, as shown here.…”

High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology

“…Our representative population of C57BL/6J data is now publicly available at <http:// www.civm.duhs.duke.edu/pubs/supplemental/NeuroImage200701/index.html>. Additional data are online, published as supplementary material (Badea et al, 2007), (Badea, A., et al, Computational anatomy in the C57BL/6J mouse brain, submitted to NeuroImage 2007). The staining and scanning protocols have been streamlined.…”