ESI mutagenesis: a one-step method for introducing mutations into bacterial artificial chromosomes.


Journal

Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869

Informations de publication

Date de publication:
02 2021
Historique:
received: 01 07 2020
revised: 23 11 2020
accepted: 23 11 2020
entrez: 9 12 2020
pubmed: 10 12 2020
medline: 14 9 2021
Statut: epublish

Résumé

Bacterial artificial chromosome (BAC)-based transgenes have emerged as a powerful tool for controlled and conditional interrogation of protein function in higher eukaryotes. Although homologous recombination-based recombineering methods have streamlined the efficient integration of protein tags onto BAC transgenes, generating precise point mutations has remained less efficient and time-consuming. Here, we present a simplified method for inserting point mutations into BAC transgenes requiring a single recombineering step followed by antibiotic selection. This technique, which we call exogenous/synthetic intronization (ESI) mutagenesis, relies on co-integration of a mutation of interest along with a selectable marker gene, the latter of which is harboured in an artificial intron adjacent to the mutation site. Cell lines generated from ESI-mutated BACs express the transgenes equivalently to the endogenous gene, and all cells efficiently splice out the synthetic intron. Thus, ESI mutagenesis provides a robust and effective single-step method with high precision and high efficiency for mutating BAC transgenes.

Identifiants

pubmed: 33293335
pii: 4/2/e202000836
doi: 10.26508/lsa.202000836
pmc: PMC7756954
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : European Research Council
ID : 638197
Pays : International

Informations de copyright

© 2020 Rondelet et al.

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Auteurs

Arnaud Rondelet (A)

Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Andrei Pozniakovsky (A)

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.

Devika Namboodiri (D)

Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Richard Cardoso da Silva (R)

Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Divya Singh (D)

Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Marit Leuschner (M)

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.

Ina Poser (I)

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.

Andrea Ssykor (A)

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.

Julian Berlitz (J)

Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Nadine Schmidt (N)

Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Lea Röhder (L)

Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Gerben Vader (G)

Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Anthony A Hyman (AA)

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.

Alexander W Bird (AW)

Max Planck Institute of Molecular Physiology, Dortmund, Germany alex.bird@mpi-dortmund.mpg.de.

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Classifications MeSH