Makita et al, 2008 determined that TAZ is essential for developmental mechanisms involved in renal and pulmonary organogenesis and that its dysfunction may be a pathogenic mechanism in common human disease. Inactivation of TAZ in mice resulted in pathological changes in the kidney and lung that resemble the common human diseases polycystic kidney disease and pulmonary emphysema. After birth, only one-fifth of TAZ-deficient homozygotes grew to adulthood and demonstrated multicystic kidneys with severe urinary concentrating defects and polyuria. Furthermore, adult TAZ-deficient homozygotes exhibited diffuse emphysematous changes in the lung.
TAZ, a transcriptional co-activator with a PDZ-binding motif (also called WWTR1) is a 14-3-3-binding molecule. TAZ acts as a co-activator for several transcription factors as well as a modulator of membrane-associated PDZ domain-containing proteins, but its physiological roles remain unknown.
The coexistence of renal and pulmonary defects observed in TAZ-deficient mice hasn’t been observed before. TAZ may have a role in a pathway common to pulmonary and renal development and so further investigation could uncover a common mechanism for organogenesis and pathogenesis of human diseases. That said, is this phenotype limited to a single mouse model and due to the specific genetic background or could the similarities observed between this phenotype and BHD Syndrome suggest any mechanistic overlap between TAZ and FLCN?
www.BHDsyndrome.org – the primary reference site for anyone interested in BHD Syndrome
Makita R et al, 2008. Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ. Am J Physiol Renal Physiol. Mar; 294(3):F542-53.
