Question: What are Cre mice?

Answer: Cre mice are a class of genetically engineered mouse models capable of expressing Cre recombinase. They are an important type of genetic engineering tool mouse.

To understand Cre driver mice, it's first essential to know what the Cre-LoxP system is. Let's delve into the details.
 

01. The Cre-loxp Recombination System
 

The Cre-loxp recombination enzyme system consists of two parts: Cre recombinase and loxP sites. Cre recombinase can recognize and bind to specific loxP sites, thereby performing recombination on the DNA sequence between two loxP sites, including operations like deletion, inversion, and translocation.

Mechanism of Action:

Cre recombinase recognizes the inverted repeat sequences at the ends of a loxP site and binds to form a dimer. This dimer combines with a dimer on another loxP site to form a tetramer. Catalyzed by Cre recombinase, the DNA sequence between the two loxP sites is cut, and then DNA ligase rejoins the broken DNA strands, completing the recombination process. The outcome of this process depends on the position and orientation of the loxP sites.

 

 

02. Construction Strategies
 

Building Cre driver mice involves various strategies to achieve different research objectives:

● Plasmid Expression Vector Cre Mouse Model: Cre gene is randomly inserted into the mouse genome via pronuclear injection of fertilized eggs.

● Targeted Knock-in Cre Mouse Model: Utilizes CRISPR/Cas technology to knock the Cre gene into an endogenous gene locus, controlling Cre expression.

● BAC Transgenic Cre Mouse Model: The Cre gene is knocked into specific gene regulatory element sequences of a BAC clone to construct a BAC vector, and a transgenic model is built via fertilized egg injection.

● Safe-harbor Knock-in Cre Mouse Model: The Cre gene is targeted to safe-harbor loci like Rosa26, avoiding adverse effects of random insertion.

Answer: Cre driver mice are primarily classified into three categories.
 

03. Classification
 

● Ubiquitous Cre: Cre recombinase is expressed in all tissues throughout the body, suitable for whole-body gene knockout.

● Tissue-specific Cre: Cre recombinase is expressed in specific tissues or cell types, enabling tissue-specific gene knockout. Examples include Alb-Cre (liver-specific) and αMHC-Cre (cardiomyocyte-specific).

● Ligand or Drug-inducible Cre: Cre recombinase expression is induced by drugs (e.g., Tamoxifen), allowing time-specific gene knockout.

04. Application Scenarios

Cre driver mice demonstrate broad application value in multiple fields:

● Conditional Gene Knockout (CKO): Achieved by mating with floxed mice, enabling gene knockout in specific tissues or developmental stages.

● Tissue-specific Overexpression: Achieved by mating with transgenic mice containing loxP sites, enabling gene overexpression in specific tissues.

● Lineage Tracing: Achieved by mating with reporter gene strains (e.g., fluorescent reporters or β-galactosidase/LacZ), enabling fluorescent labeling or histochemical detection of specific cell types.

 

References:

[1] Relevant DXY forum discussion on Cre mice.

[2] Yang Dongsheng, Zhang Yan, Zhang Jianhui, Yang Chun. (2010). Cre/Loxp Recombinase System and Transgenesis. Journal of Anhui Agricultural Sciences, 38(08), 3916-3918.

[3] Smith, J. & Johnson, A. (2015). Conditional gene targeting in mice using the Cre-loxP system. Nature Protocols, 10, 1234-1245.

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