Linking spatial gene expression patterns to sex-specific brain structural changes on a mouse model of 16p11.2 hemideletion

Translational Psychiatry
Vinod Jangir KumarThomas Nickl-Jockschat

Abstract

Neurodevelopmental disorders, such as ASD and ADHD, affect males about three to four times more often than females. 16p11.2 hemideletion is a copy number variation that is highly associated with neurodevelopmental disorders. Previous work from our lab has shown that a mouse model of 16p11.2 hemideletion (del/+) exhibits male-specific behavioral phenotypes. We, therefore, aimed to investigate with magnetic resonance imaging (MRI), whether del/+ animals also exhibited a sex-specific neuroanatomical endophenotype. Using the Allen Mouse Brain Atlas, we analyzed the expression patterns of the 27 genes within the 16p11.2 region to identify which gene expression patterns spatially overlapped with brain structural changes. MRI was performed ex vivo and the resulting images were analyzed using Voxel-based morphometry for T1-weighted sequences and tract-based spatial statistics for diffusion-weighted images. In a subsequent step, all available in situ hybridization (ISH) maps of the genes involved in the 16p11.2 hemideletion were aligned to Waxholm space and clusters obtained by sex-specific group comparisons were analyzed to determine which gene(s) showed the highest expression in these regions. We found pronounced sex-specific changes ...Continue Reading

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Citations

Dec 28, 2018·Human Molecular Genetics·Thomas ArbogastNicholas Katsanis
Dec 25, 2019·Journal of Neuroscience Research·Adele Mossa, M Chiara Manzini
Aug 29, 2020·Autism Research : Official Journal of the International Society for Autism Research·Joseph F LynchTed Abel
Nov 16, 2018·Experimental Neurobiology·Se Jin JeonChan Young Shin
May 7, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Galen MissigWilliam A Carlezon
Jul 6, 2020·Nature Communications·Jakob SeidlitzArmin Raznahan
Mar 22, 2019·Neuron·Claudia Bagni, R Suzanne Zukin
Dec 18, 2018·Psychiatry Research. Neuroimaging·Paul A RowleyJohn-Paul J Yu
Jun 24, 2021·NeuroImage. Clinical·Hildegard JanouschekThomas Nickl-Jockschat

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Software Mentioned

randomize
Waxholm
FSL statistics ( TBSS )
NIFTI
TBSS
Allen Mouse Brain Explorer
Allen Brain Explorer
Allen
FSL
Allen Mouse Brain Atlas

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