CRISPR-Cas9-mediated generation of obese and diabetic mouse models

Jae Il Roh; Junghoon Lee; Seong Uk Park; Young Shin Kang; Jaehoon Lee; Ah Reum Oh; Dong Joon Choi; Ji Young Cha; Han Woong Lee

doi:10.1538/expanim.17-0123

CRISPR-Cas9-mediated generation of obese and diabetic mouse models

Jae Il Roh, Junghoon Lee, Seong Uk Park, Young Shin Kang, Jaehoon Lee, Ah Reum Oh, Dong Joon Choi, Ji Young Cha, Han Woong Lee

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19 Citations (Scopus)

Abstract

Mouse models of obesity (ob/ob) and diabetes (db/db) in which the leptin (Lep) and leptin receptor (Lepr) genes have been mutated, respectively, have contributed to a better understanding of human obesity and type 2 diabetes and to the prevention, diagnosis, and treatment of these metabolic diseases. In this study, we report the first CRISPR-Cas9-induced Lep and Lepr knockout (KO) mouse models by co-microinjection of Cas9 mRNA and sgRNAs that specifically targeted Lep or Lepr in C57BL/6J embryos. Our newly established Lep and Lepr KO mouse models showed phenotypic disorders nearly identical to those found in ob/ob and db/db mice, such as an increase in body weight, hyperglycemia, and hepatic steatosis. Thus, Cas9-generated Lep and Lepr KO mouse lines will be easier for genotyping, to maintain the lines, and to use for future obesity and diabetes research.

Original language	English
Pages (from-to)	229-237
Number of pages	9
Journal	Experimental Animals
Volume	67
Issue number	2
DOIs	https://doi.org/10.1538/expanim.17-0123
Publication status	Published - 2018

Bibliographical note

Funding Information:
This work was supported by grants from the national

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (NRF) grants funded by the Korean government (MEST; 2010–0020878, 2012R1A1A2009607, 2015R1A2A1A01003845), the Ministry of Food and Drug Safety (14182MFDS978), a Korea Healthcare Technology R&D Project from the Ministry for Health and Welfare and Family Affairs (A085136) (to H-W Lee), the Ministry of Food and Drug Safety (14182MFDS978), and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2016R1A2B4015866; to J-Y Cha).

Publisher Copyright:
© 2018 Japanese Association for Laboratory Animal Science.

All Science Journal Classification (ASJC) codes

Animal Science and Zoology
Biochemistry, Genetics and Molecular Biology(all)
veterinary(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1538/expanim.17-0123

Cite this

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title = "CRISPR-Cas9-mediated generation of obese and diabetic mouse models",

abstract = "Mouse models of obesity (ob/ob) and diabetes (db/db) in which the leptin (Lep) and leptin receptor (Lepr) genes have been mutated, respectively, have contributed to a better understanding of human obesity and type 2 diabetes and to the prevention, diagnosis, and treatment of these metabolic diseases. In this study, we report the first CRISPR-Cas9-induced Lep and Lepr knockout (KO) mouse models by co-microinjection of Cas9 mRNA and sgRNAs that specifically targeted Lep or Lepr in C57BL/6J embryos. Our newly established Lep and Lepr KO mouse models showed phenotypic disorders nearly identical to those found in ob/ob and db/db mice, such as an increase in body weight, hyperglycemia, and hepatic steatosis. Thus, Cas9-generated Lep and Lepr KO mouse lines will be easier for genotyping, to maintain the lines, and to use for future obesity and diabetes research.",

author = "Roh, {Jae Il} and Junghoon Lee and Park, {Seong Uk} and Kang, {Young Shin} and Jaehoon Lee and Oh, {Ah Reum} and Choi, {Dong Joon} and Cha, {Ji Young} and Lee, {Han Woong}",

note = "Funding Information: This work was supported by grants from the national Funding Information: This work was supported by grants from the National Research Foundation of Korea (NRF) grants funded by the Korean government (MEST; 2010–0020878, 2012R1A1A2009607, 2015R1A2A1A01003845), the Ministry of Food and Drug Safety (14182MFDS978), a Korea Healthcare Technology R&D Project from the Ministry for Health and Welfare and Family Affairs (A085136) (to H-W Lee), the Ministry of Food and Drug Safety (14182MFDS978), and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2016R1A2B4015866; to J-Y Cha). Publisher Copyright: {\textcopyright} 2018 Japanese Association for Laboratory Animal Science.",

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AU - Roh, Jae Il

AU - Lee, Junghoon

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AU - Kang, Young Shin

AU - Lee, Jaehoon

AU - Oh, Ah Reum

AU - Choi, Dong Joon

AU - Cha, Ji Young

AU - Lee, Han Woong

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N2 - Mouse models of obesity (ob/ob) and diabetes (db/db) in which the leptin (Lep) and leptin receptor (Lepr) genes have been mutated, respectively, have contributed to a better understanding of human obesity and type 2 diabetes and to the prevention, diagnosis, and treatment of these metabolic diseases. In this study, we report the first CRISPR-Cas9-induced Lep and Lepr knockout (KO) mouse models by co-microinjection of Cas9 mRNA and sgRNAs that specifically targeted Lep or Lepr in C57BL/6J embryos. Our newly established Lep and Lepr KO mouse models showed phenotypic disorders nearly identical to those found in ob/ob and db/db mice, such as an increase in body weight, hyperglycemia, and hepatic steatosis. Thus, Cas9-generated Lep and Lepr KO mouse lines will be easier for genotyping, to maintain the lines, and to use for future obesity and diabetes research.

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CRISPR-Cas9-mediated generation of obese and diabetic mouse models

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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