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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.

SUBMITTER: Roh JI

PROVIDER: S-EPMC5955754 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Roh Jae-Il JI Lee Junghoon J Park Seong Uk SU Kang Young-Shin YS Lee Jaehoon J Oh Ah-Reum AR Choi Dong Joon DJ Cha Ji-Young JY Lee Han-Woong HW

Experimental animals 20180116 2

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 ...[more]

PMID: 29343656

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