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

Nickl-Jockschat, T., Kumar Jangir, V., Grissom, N., Welsh, S., Schoch, H., Bowman, N., et al. (2018). Linking spatial gene expression patterns to sex-specific brain structural changes on a mouse model of 16p11.2 hemideletion. In 48th Annual Meeting of the Society for Neuroscience (Neuroscience 2018).

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-633A-E Version Permalink: http://hdl.handle.net/21.11116/0000-0002-633B-D
Genre: Meeting Abstract

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Nickl-Jockschat, T, Author
Kumar Jangir, V1, 2, Author              
Grissom, NM, Author
Welsh , S, Author
Schoch, H, Author
Bowman , NM, Author
Havekes, R, Author
Kumar, M, Author
Pickup, S, Author
Poptani, H, Author
Reyes, EM, Author
Hawrylycz, TJ, Author
Abel, T, Author
Affiliations:
1Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497796              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

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 Abstract: Neurodevelopmental disorders, such as ASD and ADHD, affect males about 3-4 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-weighed sequences and tract-based spatial statistics for diffusion-weighed 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 in male animals with increased fractional anisotropy in medial fiber tracts, especially in those proximate to the striatum. Moreover, we were able to identify gene expression patterns spatially overlapping with male-specific structural changes that were associated with neurite outgrowth and the MAPK pathway. Of note, previous molecular studies have found convergent changes that point to a sex-specific dysregulation of MAPK signaling. This convergent evidence supports the idea that ISH maps can be used to meaningfully analyze imaging data sets.

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 Dates: 2018-11
 Publication Status: Published online
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Title: 48th Annual Meeting of the Society for Neuroscience (Neuroscience 2018)
Place of Event: San Diego, CA, USA
Start-/End Date: 2018-11-03 - 2018-11-07

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Title: 48th Annual Meeting of the Society for Neuroscience (Neuroscience 2018)
Source Genre: Proceedings
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Pages: - Volume / Issue: - Sequence Number: 537.07 Start / End Page: - Identifier: -