Modification of single-nucleotide polymorphism in a fully humanized CYP3A mouse by genome editing technology

Abe, Satoshi; Kobayashi, Kaoru; Oji, Asami; Sakuma, Tetsushi; Kazuki, Kanako; Takehara, Shoko; Nakamura, Kazuomi; Okada, Azusa; Tsukazaki, Yasuko; Senda, Naoto; Honma, Kazuhisa; Yamamoto, Takashi; Ikawa, Masahito; Chiba, Kan; Oshimura, Mitsuo; Kazuki, Yasuhiro

doi:https://doi.org/10.1038/s41598-017-15033-0

Modification of single-nucleotide polymorphism in a fully humanized CYP3A mouse by genome editing technology

Abe, Satoshi; Kobayashi, Kaoru; Oji, Asami et al.

Scientific Reports, 2017, 7(1), 15189

Number of Access:1,706（2025-08-18 05:06 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78578

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Title	Modification of single-nucleotide polymorphism in a fully humanized CYP3A mouse by genome editing technology
Creator	CreatorName Abe, Satoshi
	NRID 1000030255864 1000030255864 CreatorName Kobayashi, Kaoru
	NRID 1000050803417 1000050803417 CreatorName Oji, Asami
	NRID 1000090711143 1000090711143 CreatorName Sakuma, Tetsushi
	NRID 1000000774043 1000000774043 CreatorName Kazuki, Kanako
	CreatorName Takehara, Shoko
	NRID 1000090598137 1000090598137 CreatorName Nakamura, Kazuomi
	CreatorName Okada, Azusa
	CreatorName Tsukazaki, Yasuko
	CreatorName Senda, Naoto
	CreatorName Honma, Kazuhisa
	CreatorName Yamamoto, Takashi
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 CreatorName Ikawa, Masahito
	NRID 1000040159033 1000040159033 CreatorName Chiba, Kan
	NRID 1000020111619 1000020111619 CreatorName Oshimura, Mitsuo
	NRID 1000090403401 1000090403401 CreatorName Kazuki, Yasuhiro
Description	Abe, S., Kobayashi, K., Oji, A. et al. Modification of single-nucleotide polymorphism in a fully humanized CYP3A mouse by genome editing technology. Sci Rep 7, 15189 (2017). https://doi.org/10.1038/s41598-017-15033-0
Abstract	Cytochrome P450, family 3, subfamily A (CYP3A) enzymes metabolize approximately 50% of commercially available drugs. Recently, we developed fully humanized transchromosomic (Tc) CYP3A mice with the CYP3A cluster including CYP3A4, CYP3A5, CYP3A7, and CYP3A43. Our humanized CYP3A mice have the CYP3A5∗3 (g.6986G) allele, resulting in the almost absence of CYP3A5 protein expression in the liver and intestine. To produce model mice for predicting CYP3A5′s contribution to pharmacokinetics, we performed a single-nucleotide polymorphism (SNP) modification of CYP3A5 (g.6986G to A,∗3 to∗1) on the CYP3A cluster using genome editing in both mouse ES cells and fertilized eggs, and produced humanized CYP3A5∗1 mice recapitulating the CYP3A5∗1 carrier phenotype in humans. The humanized CYP3A mouse with CYP3A5∗1 is the first Tc mouse for predicting the SNP effect on pharmacokinetics in humans. The combination of Tc technology and genome editing enables the production of useful humanized models that reflect humans with different SNPs.
Publisher	Nature Research
Source Title	Scientific Reports
Volume (Issue)	7(1)
Page	15189
Date of Issued	2017-11-09
Language	English
Handle URL	https://hdl.handle.net/11094/78578
eISSN	20452322
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41598-017-15033-0
Relation.isIdenticalTo	PMID 29123154
Access Rights	open access
CopyRight	© 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Scientific Reports. 2017, 7(1), p. 15189
DC.title	Modification of single-nucleotide polymorphism in a fully humanized CYP3A mouse by genome editing technology
DC.creator	Abe, Satoshi
	Kobayashi, Kaoru
	Oji, Asami
	Sakuma, Tetsushi
	Kazuki, Kanako
	Takehara, Shoko
	Nakamura, Kazuomi
	Okada, Azusa
	Tsukazaki, Yasuko
	Senda, Naoto
	Honma, Kazuhisa
	Yamamoto, Takashi
	Ikawa, Masahito
	Chiba, Kan
	Oshimura, Mitsuo
	Kazuki, Yasuhiro
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2017-11-09
DC.identifier	https://doi.org/10.1038/s41598-017-15033-0
DC.description	Abe, S., Kobayashi, K., Oji, A. et al. Modification of single-nucleotide polymorphism in a fully humanized CYP3A mouse by genome editing technology. Sci Rep 7, 15189 (2017). https://doi.org/10.1038/s41598-017-15033-0
DCTERMS.abstract	Cytochrome P450, family 3, subfamily A (CYP3A) enzymes metabolize approximately 50% of commercially available drugs. Recently, we developed fully humanized transchromosomic (Tc) CYP3A mice with the CYP3A cluster including CYP3A4, CYP3A5, CYP3A7, and CYP3A43. Our humanized CYP3A mice have the CYP3A5∗3 (g.6986G) allele, resulting in the almost absence of CYP3A5 protein expression in the liver and intestine. To produce model mice for predicting CYP3A5′s contribution to pharmacokinetics, we performed a single-nucleotide polymorphism (SNP) modification of CYP3A5 (g.6986G to A,∗3 to∗1) on the CYP3A cluster using genome editing in both mouse ES cells and fertilized eggs, and produced humanized CYP3A5∗1 mice recapitulating the CYP3A5∗1 carrier phenotype in humans. The humanized CYP3A mouse with CYP3A5∗1 is the first Tc mouse for predicting the SNP effect on pharmacokinetics in humans. The combination of Tc technology and genome editing enables the production of useful humanized models that reflect humans with different SNPs.
DC.rights	© 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	78578
citation_title	Modification of single-nucleotide polymorphism in a fully humanized CYP3A mouse by genome editing technology
citation_author	Abe, Satoshi
	Kobayashi, Kaoru
	Oji, Asami
	Sakuma, Tetsushi
	Kazuki, Kanako
	Takehara, Shoko
	Nakamura, Kazuomi
	Okada, Azusa
	Tsukazaki, Yasuko
	Senda, Naoto
	Honma, Kazuhisa
	Yamamoto, Takashi
	Ikawa, Masahito
	Chiba, Kan
	Oshimura, Mitsuo
	Kazuki, Yasuhiro
citation_publisher	Nature Research
citation_language	English
citation_date	2017-11-09
citation_journal_title	Scientific Reports
citation_volume	7
citation_issue	1
citation_firstpage	15189
citation_doi	https://doi.org/10.1038/s41598-017-15033-0
citation_pmid	29123154
citation_public_url	https://hdl.handle.net/11094/78578

Modification of single-nucleotide polymorphism in a fully humanized CYP3A mouse by genome editing technology

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