NDLI: Generation of outbred Ace2 knockout mice by RNA transfection of TALENs displaying colitis reminiscent pathophysiology and inflammation

Content Provider	Springer Nature Link
Author	Liu, Chuxin Xiao, Liping Li, Feida Zhang, Huanhuan Li, Qin Liu, Huan Fu, Shujin Li, Chao Zhang, Xingju Wang, Jun Staunstrup, Nicklas H. Li, Yong Yang, Huanming
Copyright Year	2014
Abstract	The angiotensin I converting enzyme 2 (ACE2) is a key factor in the maintenance of intestinal homeostasis. Dysregulation of homeostasis can lead to inflammation of the colon (colitis), which can cause life-threatening enfeeblement or even cancer. Animal models are valuable surrogates in deciphering the pathology behind such human conditions and for screening of putative therapeutic targets or treatment paradigms. However, development of disease models can be time-consuming and technical demanding, which might hamper their application-value. In this study, we genetically disrupted the mouse Ace2 gene by direct injection of in vitro transcribed mRNA coding for transcription activator-like effector nucleases (TALENs) into the cytoplasm of outbred Kunming mouse zygotes. Consequently, somatic mutations were induced with an efficiency of 57 %, of which 39 % were frameshift mutations. Moreover, all modifications were stably transferred during germline transmission. In Ace2-knockout male mice (Ace2 $^{−/y }$), we observed severe chemical induced colitis, characterized by considerable weight loss, diarrhea and a shortened colon length. Histologically, Ace2 mutations resulted in the infiltration of leukocytes and the overt damage of the intestinal mucosal barrier. In addition, we detected an increased expression of inflammatory cytokines in the colon tissue of Ace2 $^{−/y }$ mice. Collectively, the data indicate that high targeting efficiency and heritability can be achieved in an outbred mouse model by zygote injection of TALEN mRNA. Furthermore, the generated Ace2 $^{−/y }$ mice display phenotypic traits reminiscent of colitis and we anticipate that such mice can be of value in studies of the intestinal microbiome or fecal transplantation.
Starting Page	433
Ending Page	446
Page Count	14
File Format	PDF
ISSN	09628819
Journal	Transgenic Research
Volume Number	24
Issue Number	3
e-ISSN	15739368
Language	English
Publisher	Springer International Publishing
Publisher Date	2014-12-02
Publisher Place	Cham
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Ace2 TALEN Gene knockout Colitis Animal model Molecular Medicine Plant Genetics & Genomics Animal Genetics and Genomics Plant Sciences Transgenics
Content Type	Text
Resource Type	Article
Subject	Genetics Animal Science and Zoology Biotechnology Agronomy and Crop Science

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