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A transgenic mouse line for assaying tissue-specific changes in endoplasmic reticulum proteostasis
Reinis Svarcbahs1, Sarah M Blossom1, Helena S Baffoe-Bonnie1
1Cellular Stress and Inflammation Section, Intramural Research Program, National Institute On Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
Transgenic Research
|May 3, 2023
Summary
Researchers developed a new mouse model to track endoplasmic reticulum (ER) protein secretion (exodosis) in specific cells. This tool helps study ER calcium imbalance and related diseases.
Area of Science:
- Cell Biology
- Neuroscience
- Biochemistry
Background:
- Calcium homeostasis is crucial for endoplasmic reticulum (ER) function.
- Cellular stress can disrupt ER calcium levels, leading to ER-resident protein secretion (exodosis).
- Monitoring exodosis offers insights into ER homeostasis and proteostasis under stress.
Purpose of the Study:
- To develop a Cre-dependent transgenic mouse model for monitoring cell-type specific exodosis in vivo.
- To characterize the expression and utility of the SERCaMP reporter system in different tissues and cell types.
- To validate the model's response to pharmacological ER calcium depletion.
Main Methods:
- Generation of LoxP-STOP-LoxP (LSL)-SERCaMP transgenic mice.
- Crossing LSL-SERCaMP mice with Cre-driver lines (Alb-Cre and DAT-Cre).
- Characterization of Gaussia luciferase (GLuc)-SERCaMP expression in organs and extracellular fluids.
- Monitoring GLuc-SERCaMP secretion after pharmacological ER calcium depletion.
Main Results:
- GLuc-SERCaMP expression was detected in liver/blood (Alb-Cre) and dopaminergic neurons/projections (DAT-Cre).
- ER calcium depletion led to increased GLuc signal in plasma (Alb-Cre) and cerebrospinal fluid (DAT-Cre).
- The model successfully monitored cell-type specific exodosis in response to ER calcium stress.
Conclusions:
- The LSL-SERCaMP mouse model enables real-time, cell-type specific monitoring of exodosis.
- This tool facilitates the study of ER calcium dysregulation in disease pathogenesis.
- The model may aid in identifying novel therapeutics and biomarkers for diseases involving ER stress.
