Expression of transgenic biotin ligases in inducible neuronal murine cell lines by integration into the mHipp11 gene locus.

Biotin proximity labeling is a powerful method for identifying proteins associated with a specific organelle, a bait protein, or RNA. It requires the expression of a modified biotin ligase by transient transfection or from a stably integrated expression construct. Because such stable integration of...

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Main Authors: Lisa Feicht, Aaron Dangel, Ralf-Peter Jansen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0315806
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author Lisa Feicht
Aaron Dangel
Ralf-Peter Jansen
author_facet Lisa Feicht
Aaron Dangel
Ralf-Peter Jansen
author_sort Lisa Feicht
collection DOAJ
description Biotin proximity labeling is a powerful method for identifying proteins associated with a specific organelle, a bait protein, or RNA. It requires the expression of a modified biotin ligase by transient transfection or from a stably integrated expression construct. Because such stable integration of transgenes into stem cells can lead to silencing during differentiation, targeting a biotin ligase to a genomic safe harbor site would be beneficial. Here, we report on the successful targeting and expression of two biotin ligase constructs to the mouse Hipp11 locus during neuronal differentiation. While randomly integrated MicroID and TurboID are expressed and active in mouse embryonic stem cells (mESCs), expression ceases upon differentiation into mESC-derived neurons, which is independent of the promoter used. In contrast, targeting of the same expression cassette to the mHipp11 locus results in expression, correct localization, and biotinylation activity not only in mESCs but also in neurons 8-10 days after differentiation. This demonstrates that the mouse Hipp11 locus is a promising genomic integration site for transgenic biotin ligases in mESCs and mESC-derived neurons.
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spelling doaj-art-e1bd9aed6530433583e56793b5a0b7a42025-08-20T02:15:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01203e031580610.1371/journal.pone.0315806Expression of transgenic biotin ligases in inducible neuronal murine cell lines by integration into the mHipp11 gene locus.Lisa FeichtAaron DangelRalf-Peter JansenBiotin proximity labeling is a powerful method for identifying proteins associated with a specific organelle, a bait protein, or RNA. It requires the expression of a modified biotin ligase by transient transfection or from a stably integrated expression construct. Because such stable integration of transgenes into stem cells can lead to silencing during differentiation, targeting a biotin ligase to a genomic safe harbor site would be beneficial. Here, we report on the successful targeting and expression of two biotin ligase constructs to the mouse Hipp11 locus during neuronal differentiation. While randomly integrated MicroID and TurboID are expressed and active in mouse embryonic stem cells (mESCs), expression ceases upon differentiation into mESC-derived neurons, which is independent of the promoter used. In contrast, targeting of the same expression cassette to the mHipp11 locus results in expression, correct localization, and biotinylation activity not only in mESCs but also in neurons 8-10 days after differentiation. This demonstrates that the mouse Hipp11 locus is a promising genomic integration site for transgenic biotin ligases in mESCs and mESC-derived neurons.https://doi.org/10.1371/journal.pone.0315806
spellingShingle Lisa Feicht
Aaron Dangel
Ralf-Peter Jansen
Expression of transgenic biotin ligases in inducible neuronal murine cell lines by integration into the mHipp11 gene locus.
PLoS ONE
title Expression of transgenic biotin ligases in inducible neuronal murine cell lines by integration into the mHipp11 gene locus.
title_full Expression of transgenic biotin ligases in inducible neuronal murine cell lines by integration into the mHipp11 gene locus.
title_fullStr Expression of transgenic biotin ligases in inducible neuronal murine cell lines by integration into the mHipp11 gene locus.
title_full_unstemmed Expression of transgenic biotin ligases in inducible neuronal murine cell lines by integration into the mHipp11 gene locus.
title_short Expression of transgenic biotin ligases in inducible neuronal murine cell lines by integration into the mHipp11 gene locus.
title_sort expression of transgenic biotin ligases in inducible neuronal murine cell lines by integration into the mhipp11 gene locus
url https://doi.org/10.1371/journal.pone.0315806
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AT ralfpeterjansen expressionoftransgenicbiotinligasesininducibleneuronalmurinecelllinesbyintegrationintothemhipp11genelocus