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Neural plate targeting by in utero nanoinjection (NEPTUNE) reveals a role for Sptbn2 in neurulation and abdominal wall closure

Katrin Mangold, View ORCID ProfileJan Mašek, Jingyan He, View ORCID ProfileUrban Lendahl, View ORCID ProfileElaine Fuchs, View ORCID ProfileEmma R Andersson
doi: https://doi.org/10.1101/2020.05.28.115972
Katrin Mangold
1Karolinska Institutet, Stockholm, Sweden
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Jan Mašek
1Karolinska Institutet, Stockholm, Sweden
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Jingyan He
1Karolinska Institutet, Stockholm, Sweden
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Urban Lendahl
1Karolinska Institutet, Stockholm, Sweden
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Elaine Fuchs
2Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York NY USA
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Emma R Andersson
1Karolinska Institutet, Stockholm, Sweden
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  • For correspondence: emma.andersson@ki.se
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ABSTRACT

Gene variants associated with disease are efficiently identified with whole genome sequencing or GWAS, but validation in vivo lags behind. We developed NEPTUNE (neural plate targeting by in utero nanoinjection), to rapidly and flexibly introduce gene expression-modifying viruses to the embryonic murine neural plate prior to neurulation, to target the future adult nervous system. Stable integration in >95% of cells in the brain enabled long-term gain- or loss-of-function, and conditional expression was achieved using mini-promotors for cell types of interest. Using NEPTUNE, we silenced Sptbn2, a gene associated with Spinocerebellar ataxia type 5 (SCA5) in humans. Silencing of Sptbn2 induced severe neural tube defects and embryo resorption, suggesting that SPTBN2 in-frame and missense deletions in SCA5 reflect hypomorphic or neomorphic functions, not loss of function. In conclusion, NEPTUNE offers a novel, rapid and cost-effective technique to test gene function in brain development, and can reveal loss of function phenotypes incompatible with life.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 28, 2020.
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Neural plate targeting by in utero nanoinjection (NEPTUNE) reveals a role for Sptbn2 in neurulation and abdominal wall closure
Katrin Mangold, Jan Mašek, Jingyan He, Urban Lendahl, Elaine Fuchs, Emma R Andersson
bioRxiv 2020.05.28.115972; doi: https://doi.org/10.1101/2020.05.28.115972
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Neural plate targeting by in utero nanoinjection (NEPTUNE) reveals a role for Sptbn2 in neurulation and abdominal wall closure
Katrin Mangold, Jan Mašek, Jingyan He, Urban Lendahl, Elaine Fuchs, Emma R Andersson
bioRxiv 2020.05.28.115972; doi: https://doi.org/10.1101/2020.05.28.115972

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