Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ

Area of Science:

• Molecular Biology
• Developmental Biology
• Genetics

Background:

• TAZ (WWTR1) is a 14-3-3-binding protein homologous to YAP.
• TAZ functions as a transcriptional coactivator and modulator of PDZ domain proteins.
• The physiological and pathological roles of TAZ are largely unknown.

Purpose of the Study:

• To investigate the role of TAZ in mammalian development and disease.
• To determine the function of TAZ in kidney and lung organogenesis.

Main Methods:

• Gene inactivation of TAZ in mice (Taz-null/lacZ knockin mutant homozygotes).
• Phenotypic analysis of TAZ-deficient mice, focusing on kidney and lung development.
• Assessment of renal function and lung morphology.

Main Results:

• TAZ gene inactivation led to severe kidney abnormalities, including cyst formation, hydronephrosis, and urinary concentrating defects, resembling polycystic kidney disease.
• TAZ-deficient adult mice exhibited diffuse emphysematous changes in the lungs, similar to pulmonary emphysema.
• Only a small fraction of TAZ-deficient homozygotes survived to adulthood.

Conclusions:

• TAZ is essential for normal kidney and lung organogenesis.
• Disruption of TAZ function during development can lead to the pathogenesis of polycystic kidney disease and pulmonary emphysema.
• TAZ plays a critical role in maintaining the structural integrity and function of the kidney and lung.