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Generation of outbred Ace2 knockout mice by RNA transfection of TALENs displaying colitis reminiscent pathophysiology and inflammation.
| Content Provider | Europe PMC |
|---|---|
| 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 |
| 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s11248-014-9855-3) contains supplementary material, which is available to authorized users. |
| Related Links | https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7102211&blobtype=pdf |
| ISSN | 09628819 |
| Journal | Transgenic Research [Transgenic Res] |
| Volume Number | 24 |
| DOI | 10.1007/s11248-014-9855-3 |
| PubMed Central reference number | PMC7102211 |
| Issue Number | 3 |
| PubMed reference number | 25448263 |
| e-ISSN | 15739368 |
| Language | English |
| Publisher | Springer International Publishing |
| Publisher Date | 2014-12-02 |
| Publisher Place | Gewerbestrasse 11, Cham, Ch 6330, Switzerland |
| Access Restriction | Open |
| Rights License | This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. © Springer International Publishing Switzerland 2014 |
| Subject Keyword | Ace2 TALEN Gene knockout Colitis Animal model |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Animal Science and Zoology Biotechnology Agronomy and Crop Science |
