Microcephaly with altered cortical layering in GIT1 deficiency revealed by quantitative neuroimaging.

Journal Article (Journal Article)

G Protein-Coupled Receptor Kinase-Interacting Protein-1 (GIT1) regulates neuronal functions, including cell and axon migration and synapse formation and maintenance, and GIT1 knockout (KO) mice exhibit learning and memory deficits. We noted that male and female GIT1-KO mice exhibit neuroimaging phenotypes including microcephaly, and altered cortical layering, with a decrease in neuron density in cortical layer V. Micro-CT and magnetic resonance microscopy (MRM) were used to identify morphometric phenotypes for the skulls and throughout the GIT1-KO brains. High field MRM of actively-stained mouse brains from GIT1-KO and wild type (WT) controls (n = 6 per group) allowed segmenting 37 regions, based on co-registration to the Waxholm Space atlas. Overall brain size in GIT1-KO mice was ~32% smaller compared to WT controls. After correcting for brain size, several regions were significantly different in GIT1-KO mice relative to WT, including the gray matter of the ventral thalamic nuclei and the rest of the thalamus, the inferior colliculus, and pontine nuclei. GIT1-KO mice had reduced volume of white matter tracts, most notably in the anterior commissure (~26% smaller), but also in the cerebral peduncle, fornix, and spinal trigeminal tract. On the other hand, the basal ganglia appeared enlarged in GIT1-KO mice, including the globus pallidus, caudate putamen, and particularly the accumbens - supporting a possible vulnerability to addiction. Volume based morphometry based on high-resolution MRM (21.5 μm isotropic voxels) was effective in detecting overall, and local differences in brain volumes in GIT1-KO mice, including in white matter tracts. The reduced relative volume of specific brain regions suggests a critical, but not uniform, role for GIT1 in brain development, conducive to brain microcephaly, and aberrant connectivity.

Full Text

Duke Authors

Cited Authors

  • Badea, A; Schmalzigaug, R; Kim, W; Bonner, P; Ahmed, U; Johnson, GA; Cofer, G; Foster, M; Anderson, RJ; Badea, C; Premont, RT

Published Date

  • February 2021

Published In

Volume / Issue

  • 76 /

Start / End Page

  • 26 - 38

PubMed ID

  • 33010377

Pubmed Central ID

  • PMC7802083

Electronic International Standard Serial Number (EISSN)

  • 1873-5894

Digital Object Identifier (DOI)

  • 10.1016/j.mri.2020.09.023

Language

  • eng

Conference Location

  • Netherlands