Related Experiment Video
Updated: Jun 20, 2026
15:40
Forward Genetic Approach to Uncover Stress Resistance Genes in Mice — A High-throughput Screen in ES Cells
Published on: November 11, 2015
Mice lacking mPGES-1 are resistant to lithium-induced polyuria
Zhanjun Jia1, Haiping Wang, Tianxin Yang
1Univ. of Utah and VA Medical Center, Salt Lake City, UT 84132, USA.
American Journal of Physiology. Renal Physiology
|August 21, 2009
Summary
Microsomal prostaglandin E synthase-1 (mPGES-1) derived PGE(2) causes lithium-induced polyuria by reducing aquaporin-2 and NKCC2 expression. Mice lacking mPGES-1 were resistant to lithium
Area of Science:
- Nephrology
- Molecular Biology
- Pharmacology
Background:
- Cyclooxygenase-2 (COX-2) activity is crucial for lithium-induced polyuria.
- The specific terminal prostaglandin (PG) isomerase involved remains unclear.
Purpose of the Study:
- To investigate the role of microsomal prostaglandin E synthase-1 (mPGES-1) in lithium-induced polyuria.
- To assess the impact of mPGES-1 deficiency on renal function and key protein expression.
Main Methods:
- Lithium chloride (LiCl) administration to mPGES-1 +/+ and mPGES-1 -/- mice.
- Measurement of urine output, osmolality, PGE(2), and cAMP levels.
- Analysis of aquaporin-2 (AQP2) and Na-K-2Cl cotransporter (NKCC2) expression via immunoblotting, immunohistochemistry, and qRT-PCR.
Main Results:
- mPGES-1 +/+ mice developed polyuria and hyposmotic urine with elevated renal mPGES-1, PGE(2), and cAMP.
- mPGES-1 -/- mice exhibited resistance to lithium-induced polyuria and urine concentrating defects.
- Lithium treatment decreased AQP2 and NKCC2 expression in mPGES-1 +/+ mice, an effect attenuated in mPGES-1 -/- mice.
Conclusions:
- mPGES-1 derived PGE(2) mediates lithium-induced polyuria.
- PGE(2) likely inhibits AQP2 and NKCC2 expression, leading to polyuria.
- mPGES-1 is a potential therapeutic target for managing lithium-induced polyuria.
