Divergence and inheritance of neocortical heterotopia in inbred and genetically-engineered mice. (18th January 2017)

• Record Type: Journal Article
• Authors: Toia, Alyssa R.; Cuoco, Joshua A.; Esposito, Anthony W.; Ahsan, Jawad; Joshi, Alok; Herron, Bruce J.; Torres, German; Bolivar, Valerie J.; Ramos, Raddy L.
• Is Part Of: Neuroscience letters. Volume 638(2017)
• Page Start: 175
• Page End: 180
• Publication Date: 2017-01-18
• Subjects: Neocortex -- Malformation -- Heterotopia -- C57BL/6; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.12.038
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Neocortical MLH is a weakly penetrant, divergent trait among inbred mice. Homozygosity, at one or more loci, is required for the formation of heterotopia. MLH formation requires one or more C57BL/6 alleles outside of chromosome 1. MLH are present in diverse genetically-engineered lines on a C57BL/6 background. Abstract: Cortical function emerges from the intrinsic properties of neocortical neurons and their synaptic connections within and across lamina. Neurodevelopmental disorders affecting migration and lamination of the neocortex result in cognitive delay/disability and epilepsy. Molecular layer heterotopia (MLH), a dysplasia characterized by over-migration of neurons into layer I, are associated with cognitive deficits and neuronal hyperexcitability in humans and mice. The breadth of different inbred mouse strains that exhibit MLH and inheritance patterns of heterotopia remain unknown. A neuroanatomical survey of numerous different inbred mouse strains, 2 first filial generation (F1) hybrids, and one consomic strain (C57BL/6J-Chr 1 A/J /NaJ) revealed MLH only in C57BL/6 mice and the consomic strain. Heterotopia were observed in numerous genetically-engineered mouse lines on a congenic C57BL/6 background. These data indicate that heterotopia formation is a weakly penetrant trait requiring homozygosity of one or more C57BL/6 alleles outside of chromosome 1. These data are relevant toward understanding neocortical development and disorders affecting neocortical lamination.