EXPERIMENTAL MODELS

Contributor Information
- Name Helen Arthur
- Institute Newcastle University
Tool Details
- Tool name: Endoglin Floxed Mouse
- Tool type: Experimental models
- Tool sub-type: Mouse
- Disease: Hereditary Haemorrhagic Telangiectasia; Angiogenesis defects; Fibrosis defects
- Model: Conditional KO
- Conditional: Yes
- Conditional description: Floxed allele
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Genetic background and cross history: Targeting the endoglin gene with trifloxed (3fl) eng vector by homologous recombination in mouse ES cells. Endoglin exons 5 and 6 and a PGK-neo selection cassette are flanked by loxP sites. The neo cassette was removed from heterozygous Eng3fl/
mice in vivo using the Meu-Cre40 transgenic mouse. These mosaics were then crossed with wild type C57Bl/6 females to generate F2 mice and all possible recombination events were observed in the F2 generation. F2 mice had inherited the floxed Endoglin allele, but not the Meu-Cre40 transgene. - Phenotype: No phenotype in the absence of Cre activity
- Zygosity:
- Description: Endoglin is an auxiliary receptor for TGFb signalling. Heterozygous germline Endoglin mutations have been identified in patients with the vascular abnormality, Hereditary Haemorrhagic Telangiectasia. Endoglin is upregulated in endothelial cells during angiogenesis and the loss of Endoglin in [transgenic] mice results in embryonic lethality at mid-gestation. This phenotype points to an important role of Endoglin in new blood vessel formation but precludes analysis at later stages in development and in postnatal life. To bypass this limitation and allow further investigations of the function of Endoglin a transgenic mice has been generated with a floxed Endoglin allele in which loxP sites flank exons 5 and 6. Mice homozygous for this allele are normal and in the presence of appropriate Cre lines will allow time and cell specific Endoglin deletion for in vivo analysis of function in cardiovascular development and disease.
- Research area: Cancer; Tissue-specific biology; Cell biology; Genetics; Immunology; Stem cell biology
- Production details: Targeting the endoglin gene with trifloxed (3fl) eng vector by homologous recombination in mouse ES cells. Endoglin exons 5 and 6 and a PGK-neo selection cassette are flanked by loxP sites. The neo cassette was removed from heterozygous Eng3fl/Ăž mice in vivo using the Meu-Cre40 transgenic mouse. These mosaics were then crossed with wild type C57Bl/6 females to generate F2 mice and all possible recombination events were observed in the F2 generation. F2 mice had inherited the floxed Endoglin allele, but not the Meu-Cre40 transgene.
- Additional notes:
- For Research Use Only
References
- • Anderberg et al. 2013. J Exp Med. 210(3):563-79. PMID: 23401487.
- • Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination.
- • Allinson et al. 2007. Genesis. 45(6):391-5. PMID: 17506087.
- • Generation of a floxed allele of the mouse Endoglin gene.