Related Experiment Video
Updated: Aug 9, 2026
Modeling Breast Cancer via an Intraductal Injection of Cre-expressing Adenovirus into the Mouse Mammary Gland
Published on: June 7, 2019
Transgenic mice expressing tamoxifen-inducible Cre for somatic gene modification in renal epithelial cells
Irma S Lantinga-van Leeuwen1, Wouter N Leonhard, Annemieke van de Wal
1Leiden University Medical Center, Center for Human and Clinical Genetics, Leiden, The Netherlands.
Abstract:
Gene inactivation often leads to an embryonic-lethal phenotype. In focal diseases like renal cell carcinomas and polycystic kidney disease, somatic gene inactivation in subsets of cells is likely to occur at later stages. We generated a transgenic mouse line with an inducible form of Cre recombinase for conditional gene modifications in kidney epithelial cells. To this end a 1.4-kb promoter fragment of the kidney-specific cadherin gene (KspCad) was cloned upstream of a tamoxifen-inducible Cre recombinase (CreER(T2)) encoding sequence. Expression and activity of Cre was evaluated using reverse transcriptase polymerase chain reaction (RT-PCR) analysis and by crossbreeding to Z/EG reporter mice. One KspCad-CreER(T2) line showed kidney-specific Cre expression and mediated recombination upon tamoxifen treatment in Z/EG reporter mice. No reporter gene expression was detected in untreated animals or in extrarenal tissues upon treatment. Within the kidneys, enhanced green fluorescent protein (EGFP) fluorescence was observed in epithelial cells in several nephronic segments. In addition, the system successfully recombined a floxed Pkd1 gene.
Insights
Researchers developed a new transgenic mouse model for kidney research. This model allows for targeted gene modification in kidney cells, aiding studies of kidney diseases like polycystic kidney disease.
Area of Science:
- Genetics
- Molecular Biology
- Nephrology
Background:
- Gene inactivation frequently results in embryonic lethality, complicating studies of focal kidney diseases.
- Somatic gene inactivation in kidney epithelial cells is crucial for understanding diseases like renal cell carcinoma and polycystic kidney disease.
Purpose of the Study:
- To create a transgenic mouse line for inducible and kidney-specific gene modification.
- To enable conditional gene targeting in kidney epithelial cells for disease modeling.
Main Methods:
- Cloning of a kidney-specific cadherin (KspCad) promoter upstream of a tamoxifen-inducible Cre recombinase (CreER(T2)).
- Evaluation of Cre expression and activity via RT-PCR and crossbreeding with Z/EG reporter mice.
- Administration of tamoxifen to induce recombination.
Main Results:
- A KspCad-CreER(T2) transgenic mouse line exhibited kidney-specific Cre expression.
- Tamoxifen treatment induced recombination specifically in kidney epithelial cells of Z/EG reporter mice.
- Successful recombination of a floxed Pkd1 gene was demonstrated, confirming system functionality.
Conclusions:
- The KspCad-CreER(T2) mouse line provides a valuable tool for conditional gene manipulation in kidney epithelial cells.
- This model facilitates research into the genetic basis of kidney diseases.
- The system shows high specificity, with no observed recombination in extrarenal tissues.
