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Updated: Jan 30, 2026
Laser Ablation of the Zebrafish Pronephros to Study Renal Epithelial Regeneration
Published on: August 29, 2011
Tsc1 ablation in Prx1 and Osterix lineages causes renal cystogenesis in mouse
Zhixiang Wu1, Hongguang Wu1, Shafiquzzaman Md1
1Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200240, China.
Abstract:
Tuberous Sclerosis Complex (TSC) is caused by mutations in TSC1 or TSC2, which encode negative regulators of the mTOR signaling pathway. The renal abnormalities associated with TSC include angiomyolipoma, cysts, and renal cell carcinoma. Here we report that specific ablation of Tsc1 using the mesenchymal stem cell-osteoblast lineage markers induced cystogenesis in mice. Using Rosa-tdTomato mice, we found that Prx1- or Dermo1-labeled cells were present in the nephron including glomerulus but they were not stained by markers for podocytes, mesangial cells, endothelial cells, or proximal or loop of Henle tubular cells, while Osx is known to label tubular cells. Tsc1 deficiency in Prx1 lineage cells caused development of mild cysts that were positive only for Tamm-Horsfall protein (THP), a loop of Henle marker, while Tsc1 deficiency in Osx lineage cells caused development of cysts that were positive for Villin, a proximal tubular cell marker. On the other hand, Tsc1 deficiency in the Dermo1 lineage did not produce detectable phenotypical changes in the kidney. Cyst formation in Prx1-Cre; Tsc1f/f and Osx-Cre; Tsc1f/f mice were associated with increase in both proliferative and apoptotic cells in the affected tissue and were largely suppressed by rapamycin. These results suggest that Prx1 and Osx lineages cells may contribute to renal cystogenesis in TSC patients.
Insights
Tuberous Sclerosis Complex (TSC) involves kidney cysts. Ablating Tsc1 in specific kidney cell lineages (Prx1 and Osx) induced cyst formation, suggesting these cells contribute to TSC-related renal disease.
Area of Science:
- Nephrology
- Genetics
- Cell Biology
Background:
- Tuberous Sclerosis Complex (TSC) is a genetic disorder caused by mutations in TSC1 or TSC2, affecting the mTOR signaling pathway.
- Renal abnormalities in TSC include cysts, angiomyolipomas, and renal cell carcinoma.
Purpose of the Study:
- To investigate the role of specific cell lineages in TSC-associated renal cystogenesis.
- To determine if Tsc1 deficiency in distinct cell types contributes to kidney cyst formation.
Main Methods:
- Utilized genetically modified mice with targeted Tsc1 ablation in specific cell lineages (Prx1, Dermo1, Osx).
- Employed lineage tracing with Rosa-tdTomato mice and cell-specific markers (THP, Villin).
- Assessed cyst formation, proliferation, and apoptosis, and evaluated rapamycin's effect.
Main Results:
- Tsc1 ablation in Prx1 lineage cells led to cysts positive for the loop of Henle marker THP.
- Tsc1 deficiency in Osx lineage cells resulted in cysts positive for the proximal tubule marker Villin.
- Cystogenesis was linked to increased proliferation and apoptosis, and partially reversed by rapamycin.
Conclusions:
- Prx1 and Osx lineage cells contribute to renal cystogenesis in Tsc1-deficient models.
- These findings suggest specific cell types within the nephron may play a critical role in TSC renal pathology.
- Targeting mTOR signaling with rapamycin may offer therapeutic potential for TSC-related kidney disease.
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