Related Experiment Video
Updated: Oct 30, 2025
Forward Genetic Approach to Uncover Stress Resistance Genes in Mice — A High-throughput Screen in ES Cells
Published on: November 11, 2015
Induction of Stress-Induced Renal Cellular Senescence In Vitro: Impact of Mouse Strain Genetic Diversity
Chieh Ming Liao1, Vera Christine Wulfmeyer1, Maxine Swallow2
1Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany.
Abstract:
Cellular senescence, a stress-induced state of irreversible cell cycle arrest, is associated with organ dysfunction and age-related disease. While immortalized cell lines bypass key pathways of senescence, important mechanisms of cellular senescence can be studied in primary cells. Primary tubular epithelial cells (PTEC) derived from mouse kidney are highly susceptible to develop cellular senescence, providing a valuable tool for studying such mechanisms. Here, we tested whether genetic differences between mouse inbred strains have an impact on the development of stress-induced cellular senescence in cultured PTEC. Kidneys from 129S1, B6, NOD, NZO, CAST, and WSB mice were used to isolate PTEC. Cells were monitored for expression of typical senescence markers (SA-β-galactosidase, γ-H2AX+/Ki67-, expression levels of CDKN2A, lamin B1, IL-1a/b, IL-6, G/M-CSF, IFN-g, and KC) at 3 and 10 days after pro-senescent gamma irradiation. Clear differences were found between PTEC from different strains with the highest senescence values for PTEC from WSB mice and the lowest for PTEC from 129S1 mice. PTEC from B6 mice, the most commonly used inbred strain in senescence research, had a senescence score lower than PTEC from WSB and CAST mice but higher than PTEC from NZO and 129S1 mice. These data provide new information regarding the influence of genetic diversity and help explain heterogeneity in existing data. The observed differences should be considered when designing new experiments and will be the basis for further investigation with the goal of identifying candidate loci driving pro- or anti-senescent pathways.
Insights
Genetic differences between mouse strains significantly impact cellular senescence in kidney cells. WSB mice show the highest senescence, while 129S1 mice exhibit the lowest, affecting research findings.
Area of Science:
- Gerontology
- Cell Biology
- Genetics
Background:
- Cellular senescence is a key factor in organ dysfunction and age-related diseases.
- Studying senescence in primary cells is crucial as immortalized cell lines bypass critical pathways.
- Primary kidney tubular epithelial cells (PTEC) are susceptible to senescence, making them valuable research models.
Purpose of the Study:
- To investigate the impact of genetic variations among mouse inbred strains on stress-induced cellular senescence in cultured PTEC.
- To understand how genetic diversity influences senescence development and contributes to data heterogeneity in aging research.
Main Methods:
- Primary tubular epithelial cells (PTEC) were isolated from six different mouse inbred strains (129S1, B6, NOD, NZO, CAST, WSB).
- Cells were subjected to gamma irradiation to induce senescence.
- Senescence markers, including SA-β-galactosidase, γ-H2AX, Ki67, CDKN2A, lamin B1, and cytokine/chemokine profiles, were analyzed at 3 and 10 days post-irradiation.
Main Results:
- Significant differences in senescence levels were observed among PTEC from various mouse strains.
- PTEC from WSB mice displayed the highest senescence, whereas PTEC from 129S1 mice showed the lowest.
- PTEC from commonly used B6 mice had intermediate senescence levels, lower than WSB and CAST but higher than NZO and 129S1.
Conclusions:
- Genetic background strongly influences the development of stress-induced cellular senescence in mouse kidney PTEC.
- These findings highlight the importance of considering genetic diversity to explain variability in senescence research.
- The study lays the groundwork for identifying genetic loci that regulate pro- or anti-senescence pathways.
More Related Videos
09:14Evaluation of Injury-induced Senescence and In Vivo Reprogramming in the Skeletal Muscle
Published on: October 26, 2017
06:48Quantitative Real-Time Polymerase Chain Reaction Evaluation of MicroRNA Expression in Kidney and Serum of Mice with Age-Dependent Renal Impairment
Published on: April 29, 2022