Principle of Cre-DIO system

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Product list: Cre/loxP tools in AAV vector(AAV-Cre), adenoviral vector(Ad-Cre) and lentiviral vector(Lv-Cre)

Cat No.	Pre-made Cre	Viral vector	Protomer	Promoter Tissue Specificity	Promoter Tissue Specificity characteristics
GMV-AdCre-01	Ad-CMV-Cre	Adenovirus	CMV	Total	Total
GMV-AdCre-02	Ad-CMV-Cre-GFP	Adenovirus	CMV	Total	Total
GMV-AAV9Cre-01	AAV9-CMV-Cre	AAV GeneMedi offer multiple serotypes of AAV-Cre loxP system for your option: · AAV1-Cre · AAV2-Cre · AAV2 variant (Y444F)-Cre · AAV2 variant (Y272F, Y444F, Y500F, Y730F)-Cre · AAV2 variant (Y444F, Y730F, Y500F, Y272F, Y704F, Y252F)-Cre · AAV2 variant(AAV2.7m8)-Cre · AAV5-Cre · AAV6-Cre · AAV8-Cre · AAV8-1m-Cre · AAV8-2m-Cre · AAV8 variant (Y733F, Y447F, Y275)-Cre · AAV9-Cre · AAV-Rh.10-Cre · AAV-DJ-Cre · AAV-DJ/8-Cre · AAV-Retro (Retrograde)-Cre · AAV-PHP.B-Cre · AAV9-PHP.A-Cre · AAV-PHP.eB-Cre · AAV-PHP.S-Cre	CMV	Total	Total
GMV-AAV9Cre-02	AAV9-CMV-Cre-ZsGreen		CMV	Total	Total
GMV-AAV9Cre-03	AAV9-CAG-Cre		CAG	Total	Total
GMV-AAV9Cre-04	AAV9-CAG-Cre-ZsGreen		CAG	Total	Total
GMV-AAV9Cre-05	AAV9-Syn-Cre-EGFP		synapsin (SYN)	Neuro	Neuron-specific promoter
GMV-AAV9Cre-06	AAV9-Syn-Cre		synapsin (SYN)	Neuro	Neuron-specific promoter
GMV-AAV9Cre-07	AAV9-CaMKII-Cre-EGFP		CaMKII	Neuro	Forebrain glutamate neuron-specific promoter
GMV-AAV9Cre-08	AAV9-CaMKII-Cre		CaMKII	Neuro	Forebrain glutamate neuron-specific promoter
GMV-AAV9Cre-09	AAV9-GFAP-Cre-EGFP		GFAP	Neuro	Astrocyte specific promoter
GMV-AAV9Cre-10	AAV9-GFAP-Cre		GFAP	Neuro	Astrocyte specific promoter
GMV-AAV9Cre-11	AAV9-cTNT-Cre		cTnT	heart	Cardiomyocyte specific promoter
GMV-AAV9Cre-12	AAV9-cTNT-Cre-EGFP		cTnT	heart	Cardiomyocyte specific promoter
GMV-AAV9Cre-13	AAV9-TBG-Cre		TBG	liver	Hepatic specific promoter
GMV-AAV9Cre-14	AAV9-TBG-Cre-ZsGreen		TBG	liver	Hepatic specific promoter
GMV-AAV9Cre-15	AAV9-TIE-Cre		TIE	endothelial	Endothelial-specific promoter
GMV-AAV9Cre-16	AAV9-cd68-Cre		cd68	Neuro	Microglia-specific promoter
GMV-AAV9Cre-17	AAV9-c-fos-Cre		c-fos	Neuro	Excitatory neuron promoter
GMV-AAV9Cre-18	AAV9-mecp2-Cre		mecp2	Neuro	Shorter neuron-specific promoter
GMV-AAV9Cre-19	AAV9-MHCK7-Cre		MHCK7	muscle	Muscle specific promoter
GMV-AAV9Cre-20	AAV9-Rpe65-Cre		Rpe65	retina	Retinal specific promoter
GMV-AAV9Cre-21	AAV9-sm22a-Cre		sm22a	muscle	Smooth muscle specific promoter
GMV-AAV9Cre-22	AAV9-Spc5-12-Cre		Spc5-12	muscle	Myocyte specific promoter
GMV-AAV9Cre-23	AAV9-Ta1-Cre		Tal	Neuro	Early neuron-specific promoter
GMV-LvCre-01	Lv-CMV-Cre	Lentivirus	CMV	Total	Total
GMV-LvCre-02	Lv-CMV-Cre-zsgreen	Lentivirus	CMV	Total	Total

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Abstract

Cre-loxP system is widely used in the field of biosciences, especially in the generation of genetically engineered mice (knockout or overexpression), enabling researchers to study the function of gene of interest (GOI). To date, numerous systems, derived from the basic Cre-loxP system, have been developed to precisely control gene expression at desired time or cells. Here, we briefly introduce Cre-loxP system, and give a summary about its applications, especially viral vectors-mediated Cre expression (such as AAV-Cre or Ad-Cre) for in vitro or in vivo studies.

Principle of Cre-DIO

Although Cre-loxP tool is widespread in biological sciences, it is really restrictive to achieve more than one recombination event in a cell. Therefore, numerous loxP mutant versions have been created, with the variation from the unique 8 bp core asymmetric spacer "NNNTANNN", such as loxN (GtATACcT), lox2272 (GgATACtT), lox5171 (ATGTGTaC), loxM2 (AgaaAcca), loxM3 (taaTACCA), loxM11 (AGATAGAA), and lox511 (GtATACAT). These lox variants only proceed recombination with the same type of lox sites, with no ability to interact with the other types. In Cre-DIO system, there are two pairs of lox sites (lox site 1 and lox site 2) flanking inverted GOI and reporter gene. In the absence of Cre, the inverted GOI and reporter are inactivated. Upon administration of Cre, the two pairs of lox sites will undergo recombination, resulting in the expression of GOI and reporter gene. Simultaneously, the cells with recombination interaction are labeled by the reporter gene (Fig. 6). The Cre-DIO tool utilizes initially inverted GOI to truly inactivate GOI, and activates GOI after a series of recombination interactions. Compared to the traditional overexpression strategy via floxed stop, this technology is much more effective to avoid the transcriptional leakage when the stop codon fails to totally suppress the transcription of GOI.

Figure 6. Principle of Cre-DIO (double-floxed inverse open reading frame) system. Without Cre, the GOI and reporter gene are inverted and silenced. In the presence of Cre, first, the transgene will be reoriented, then one of the two lox sites in each pair will be excised. Finally, the transgene contains only an incompatible pair of lox sites (lox 2-GOI-Reporter-lox 1) that are no longer responsive to Cre. Thus, the GOI and reporter gene will be activated. Lox site 1 and lox site 2 are variants of lox sites.

Summary

The Cre-loxP system, especially inducible tissue-specific knockout and viral vector-mediated Cre expression, has been highly utilized in genetics and cell biology research. Nevertheless, it seems that Cre-loxP system will continue to be prevalent in current and future research studies. GeneMedi is proficient in viral vector development and offers kinds of viral vector-based Cre tools, we can provide the best services and products if required.

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