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A new Cre driver mouse line, Tcf21/Pod1-Cre, targets metanephric mesenchyme
Yoshiro Maezawa1, Matthew Binnie, Chengjin Li
1The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Abstract:
Conditional gene targeting in mice has provided great insight into the role of gene function in kidney development and disease. Although a number of Cre-driver mouse strains already exist for the kidney, development of additional strains with unique expression patterns is needed. Here we report the generation and validation of a Tcf21/Pod1-Cre driver strain that expresses Cre recombinase throughout the condensing and stromal mesenchyme of developing kidneys and in their derivatives including epithelial components of the nephron and interstitial cells. To test the efficiency of this line, we crossed it to mice transgenic for either loss or gain of function β-catenin conditional alleles. Mice with deletion of β-catenin from Tcf21-expressing cells are born with hypoplastic kidneys, hydroureters and hydronephrosis. By contrast, Tcf21-Cre driven gain of function for β-catenin in mice results in fused midline kidneys and hypoplastic kidneys. Finally, we report the first renal mesenchymal deletion of Patched1 (Ptch1), the receptor for sonic hedgehog (Shh), which results in renal cysts demonstrating a functional role of Shh signaling pathway in renal cystogensis. In summary, we report the generation and validation of a new Cre driver strain that provides robust excision in metanephric mesenchyme.
Insights
A new Tcf21/Pod1-Cre mouse model enables precise gene manipulation in developing kidneys. This tool aids research into kidney development and diseases like renal cysts by allowing targeted gene deletion or activation.
Area of Science:
- Nephrology
- Developmental Biology
- Genetics
Background:
- Conditional gene targeting in mice is crucial for studying kidney development and disease.
- Existing Cre-driver mouse strains for the kidney have limitations, necessitating new lines with unique expression patterns.
Purpose of the Study:
- To generate and validate a novel Tcf21/Pod1-Cre driver mouse strain for precise gene manipulation in the developing kidney.
- To investigate the roles of beta-catenin and sonic hedgehog signaling in kidney development and disease using the new Cre driver strain.
Main Methods:
- Generation and characterization of the Tcf21/Pod1-Cre driver mouse strain.
- Crossing the Tcf21/Pod1-Cre mice with conditional beta-catenin alleles (loss and gain of function).
- Performing renal mesenchymal deletion of Patched1 (Ptch1) to study sonic hedgehog signaling.
Main Results:
- The Tcf21/Pod1-Cre strain effectively expresses Cre recombinase in metanephric mesenchyme and its derivatives.
- Deletion of beta-catenin in Tcf21-expressing cells leads to hypoplastic kidneys, hydroureters, and hydronephrosis.
- Gain of function for beta-catenin results in fused midline and hypoplastic kidneys.
- Deletion of Ptch1 in the renal mesenchyme causes renal cysts, indicating a role for sonic hedgehog signaling in cystogenesis.
Conclusions:
- The Tcf21/Pod1-Cre driver strain provides robust and specific gene excision in the metanephric mesenchyme.
- This new tool facilitates the study of gene function in kidney development and disease.
- The study highlights the importance of beta-catenin and sonic hedgehog signaling pathways in renal development and pathogenesis.
