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Updated: Feb 22, 2026
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
A knock-in mouse line conditionally expressing the tumor suppressor WTX/AMER1
Agnès Boutet1, Glenda Comai1, Aurélie Charlet1
1Université Côte d'Azur, Inserm U1091, CNRS UMR 7277, iBV, France.
Abstract:
WTX/AMER1 is an important developmental regulator, mutations in which have been identified in a proportion of patients suffering from the renal neoplasm Wilms' tumor and in the bone malformation syndrome Osteopathia Striata with Cranial Sclerosis (OSCS). Its cellular functions appear complex and the protein can be found at the membrane, within the cytoplasm and the nucleus. To understand its developmental and cellular function an allelic series for Wtx in the mouse is crucial. Whereas mice carrying a conditional knock out allele for Wtx have been previously reported, a gain-of-function mouse model that would allow studying the molecular, cellular and developmental role of Wtx is still missing. Here we describe the generation of a novel mouse strain that permits the conditional activation of WTX expression. Wtx fused to GFP was introduced downstream a stop cassette flanked by loxP sites into the Rosa26 locus by gene targeting. Ectopic WTX expression is reported after crosses with several Cre transgenic mice in different embryonic tissues. Further, functionality of the fusion protein was demonstrated in the context of a Wtx null allele.
Insights
Researchers developed a new mouse model for conditional WTX/AMER1 activation, crucial for studying its complex roles in development and disease. This gain-of-function model aids understanding of Wilms
Area of Science:
- Developmental Biology
- Genetics
- Oncology
Background:
- WTX/AMER1 is a critical developmental regulator implicated in Wilms' tumor and Osteopathia Striata with Cranial Sclerosis (OSCS).
- Its complex cellular localization (membrane, cytoplasm, nucleus) and function necessitate advanced research models.
- Existing mouse models lack a gain-of-function system to study WTX/AMER1's developmental roles.
Purpose of the Study:
- To generate a novel mouse model enabling conditional activation of WTX/AMER1 expression.
- To investigate the molecular, cellular, and developmental functions of WTX/AMER1 through gain-of-function studies.
- To assess the functionality of the engineered WTX/AMER1 fusion protein.
Main Methods:
- Gene targeting to introduce WTX fused to GFP downstream of a floxed stop cassette into the Rosa26 locus.
- Generation of a conditional gain-of-function mouse strain.
- Crossings with Cre transgenic mouse lines to achieve tissue-specific ectopic WTX/AMER1 expression.
Main Results:
- Successful generation of a mouse strain for conditional WTX/AMER1 activation.
- Demonstration of ectopic WTX/AMER1 expression in various embryonic tissues upon Cre recombination.
- Confirmation of the fusion protein's functionality, particularly in the context of a Wtx null allele.
Conclusions:
- The developed mouse model provides a valuable tool for studying WTX/AMER1's gain-of-function effects.
- This model will advance the understanding of WTX/AMER1's complex roles in embryonic development and disease.
- Further research can now explore WTX/AMER1's precise functions in various biological contexts.
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