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EIIa-iCre Mouse Model
| Strain Name | C57BL/6NMcl-Rosa26 tm1<sup>(EIIa promoter-NLS-iCre)</sup>/MCL |
|---|---|
| Strain Background | C57BL/6N |
| Editing Type | Knock-In |
| Catalog No. | M02095 |
- Systemic Gene Knockout or Activation
- Germline Recombination and Establishment of Stable Recombinant Lines
- Early Embryonic Development and Gene Function Research
By precisely inserting an expression cassette comprising the adenovirus EIIa promoter, a nuclear localisation signal (NLS) sequence and an improved Cre recombinase (iCre) into the murine Rosa26 locus, the Rosa26‑EIIa‑NLS‑iCre knock‑in allele was successfully generated. In this model, the EIIa promoter drives downstream iCre expression in oocytes, zygotes and early‑stage embryos; the NLS sequence facilitates nuclear import of the iCre recombinase, enabling recognition of loxP sites flanking floxed alleles and mediation of DNA recombination. Site‑specific integration of the expression cassette at the Rosa26 locus provides a stable, single‑copy genomic environment for exogenous Cre expression. iCre is an improved Cre recombinase with mammalian codon optimisation, which enhances its expression level and loxP recombination efficiency in murine cells<sup>[1–5]</sup>.
The EIIa promoter is derived from adenovirus early transcriptional regulatory elements. It drives Cre recombinase expression during early mouse embryonic development and mediates genetic recombination between loxP sites before the establishment of somatic cell lineages. The Rosa26 locus is widely used for site‑specific expression of exogenous genes and Cre activity reporting in mice; accordingly, Rosa26‑EIIa‑NLS‑iCre mice serve as a constitutive, early‑embryonic‑onset Cre tool line. When crossed with mice carrying floxed alleles, iCre mediates target‑sequence deletion, conditional gene knockout or reporter‑gene activation in early embryos and their progeny cells, thereby achieving systemic genetic modification. This provides a genetic tool for studying embryonic development, cell lineage formation, tissue and organ function, systemic gene actions and the mechanisms of hereditary diseases<sup>[1,2,4,5]</sup>.
References
- Lakso M, Pichel JG, Gorman JR, Sauer B, Okamoto Y, Lee E, et al. Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc Natl Acad Sci U S A. 1996;93(12):5860‑5865. doi: 10.1073/pnas.93.12.5860.
- Schwenk F, Baron U, Rajewsky K. A cre‑transgenic mouse strain for the ubiquitous deletion of loxP‑flanked gene segments including deletion in germ cells. Nucleic Acids Res. 1995;23(24):5080‑5081. doi: 10.1093/nar/23.24.5080.
- Shimshek DR, Kim J, Hübner MR, Spergel DJ, Buchholz F, Casanova E, et al. Codon‑improved Cre recombinase (iCre) expression in the mouse. Genesis. 2002;32(1):19‑26. doi: 10.1002/gene.10023.
- Soriano P. Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet. 1999;21(1):70‑71. doi: 10.1038/5007.
- Tchorz JS, Suply T, Ksiazek I, Giachino C, Cloëtta D, Danzer CP, et al. A modified RMCE‑compatible Rosa26 locus for the expression of transgenes from exogenous promoters. PLoS One. 2012;7(1):e30011. doi: 10.1371/journal.pone.0030011.
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- Broad Recombination in Early Embryos: Driven by the adenovirus EIIa promoter, iCre expression initiates Cre‑LoxP recombination at the pre‑implantation embryonic stage, enabling recombination events to be widely transmitted across multiple tissues and cell lineages. This makes the model suitable for generating systemically recombinant mice.
- Efficient Removal of LoxP‑Flanked Sequences: The EIIa promoter acts during early embryogenesis, mediating LoxP recombination prior to tissue differentiation. It is well‑suited for deleting critical fragments, blocking elements or selection markers from conditional alleles.
- Efficient Nuclear Localisation and Recombination: The NLS nuclear localisation signal facilitates iCre import into the nucleus. Codon‑optimised iCre efficiently recognises LoxP sites and mediates recombination, enhancing the deletion efficiency of target sequences.
- Site‑Specific Integration at the Rosa26 Locus: The EIIa‑NLS‑iCre expression cassette is precisely inserted into the Rosa26 safe‑harbour locus, minimising position effects and genetic instability associated with random integration. This supports stable transgene expression and reliable germline transmission.
- Inducer‑Free, Convenient Usage: This model does not require tamoxifen or other inducing agents. Recombination is mediated simply by crossing with mice carrying LoxP sites, enabling rapid generation of systemically recombinant offspring.
FAQ
Game-changing benefits？
While competitors highlight germline efficiency gains, shorter timelines and enhanced 3Rs animal welfare benefits for their technologies, these are merely incremental improvements over traditional approaches. In sharp contrast, our proprietary technology delivers fully pure, homogeneous lineages—every single cell of the mice is derived exclusively from totipotent ES cells, with guaranteed 100% germline transmission efficiency. To experience these unparalleled benefits firsthand, enquire about your custom mouse model project with us or order embryos for in-house validation at your facility.
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Who owns the mouse lP? Do l need a licence from Mingceler?
All model generation projects of Mingceler operate under a fee-for-service framework.
IP Ownership: All intellectual property rights related to custom mouse models, including derived organs, tissues, cells, and biological materials, are the sole and exclusive property of the Client.
Third-Party Transfer Permission: The Client may independently decide to retain, utilize, or commercialize their custom models project materials (e.g., targeting vectors, ES cells, mouse lines) without the need for prior consent from Mingceler.
Licensing Exemption: The Client has full autonomy over all uses of the custom models or their derivatives, including but not limited to commercialization, distribution to third parties, and publication involving model data. No written license from Mingceler is required for such uses.