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A Lipid Nanoparticle-Based Method for the Generation of Liver-Specific Knockout Mice

Knockout mice are useful tools that can provide information about the normal function of genes, including their biochemical, developmental, and physiological roles. One problem associated with the generation of knockout mice is that the loss of some genes of interest produces a lethal phenotype. The...

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Autores principales: Morita, Sumiyo, Horii, Takuro, Kimura, Mika, Kobayashi, Ryosuke, Tanaka, Hiroki, Akita, Hidetaka, Hatada, Izuho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10532048/
https://www.ncbi.nlm.nih.gov/pubmed/37762602
http://dx.doi.org/10.3390/ijms241814299
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author Morita, Sumiyo
Horii, Takuro
Kimura, Mika
Kobayashi, Ryosuke
Tanaka, Hiroki
Akita, Hidetaka
Hatada, Izuho
author_facet Morita, Sumiyo
Horii, Takuro
Kimura, Mika
Kobayashi, Ryosuke
Tanaka, Hiroki
Akita, Hidetaka
Hatada, Izuho
author_sort Morita, Sumiyo
collection PubMed
description Knockout mice are useful tools that can provide information about the normal function of genes, including their biochemical, developmental, and physiological roles. One problem associated with the generation of knockout mice is that the loss of some genes of interest produces a lethal phenotype. Therefore, the use of conditioned knockout mice, in which genes are disrupted in specific organs, is essential for the elucidation of disease pathogenesis and the verification of drug targets. In general, conditional knockout mice are produced using the Cre/loxP system; however, the production of the large numbers of Cre/flox knockout and control mice required for analysis requires substantial time and effort. Here, we describe the generation of liver-specific conditional knockout mice via the introduction of lipid nanoparticles encapsulating Cre mRNA into the liver of floxed mice. This technique does not require the production of offspring by mating floxed mice and is therefore more convenient than the conventional method. The results presented here demonstrate that the LNP-based method enables liver-specific gene knockout in a short period of time.
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spelling pubmed-105320482023-09-28 A Lipid Nanoparticle-Based Method for the Generation of Liver-Specific Knockout Mice Morita, Sumiyo Horii, Takuro Kimura, Mika Kobayashi, Ryosuke Tanaka, Hiroki Akita, Hidetaka Hatada, Izuho Int J Mol Sci Communication Knockout mice are useful tools that can provide information about the normal function of genes, including their biochemical, developmental, and physiological roles. One problem associated with the generation of knockout mice is that the loss of some genes of interest produces a lethal phenotype. Therefore, the use of conditioned knockout mice, in which genes are disrupted in specific organs, is essential for the elucidation of disease pathogenesis and the verification of drug targets. In general, conditional knockout mice are produced using the Cre/loxP system; however, the production of the large numbers of Cre/flox knockout and control mice required for analysis requires substantial time and effort. Here, we describe the generation of liver-specific conditional knockout mice via the introduction of lipid nanoparticles encapsulating Cre mRNA into the liver of floxed mice. This technique does not require the production of offspring by mating floxed mice and is therefore more convenient than the conventional method. The results presented here demonstrate that the LNP-based method enables liver-specific gene knockout in a short period of time. MDPI 2023-09-19 /pmc/articles/PMC10532048/ /pubmed/37762602 http://dx.doi.org/10.3390/ijms241814299 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Morita, Sumiyo
Horii, Takuro
Kimura, Mika
Kobayashi, Ryosuke
Tanaka, Hiroki
Akita, Hidetaka
Hatada, Izuho
A Lipid Nanoparticle-Based Method for the Generation of Liver-Specific Knockout Mice
title A Lipid Nanoparticle-Based Method for the Generation of Liver-Specific Knockout Mice
title_full A Lipid Nanoparticle-Based Method for the Generation of Liver-Specific Knockout Mice
title_fullStr A Lipid Nanoparticle-Based Method for the Generation of Liver-Specific Knockout Mice
title_full_unstemmed A Lipid Nanoparticle-Based Method for the Generation of Liver-Specific Knockout Mice
title_short A Lipid Nanoparticle-Based Method for the Generation of Liver-Specific Knockout Mice
title_sort lipid nanoparticle-based method for the generation of liver-specific knockout mice
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10532048/
https://www.ncbi.nlm.nih.gov/pubmed/37762602
http://dx.doi.org/10.3390/ijms241814299
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