title: Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ.
abstract: TAZ (transcriptional coactivator with PDZ-binding motif), also called WWTR1 (WW domain containing transcription regulator 1), is a 14-3-3-binding molecule homologous to Yes-associated protein. TAZ acts as a coactivator for several transcription factors as well as a modulator of membrane-associated PDZ domain-containing proteins, but its (patho)physiological roles remain unknown. Here we show that gene 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. Taz-null/lacZ knockin mutant homozygotes demonstrated renal cyst formation as early as embryonic day 15.5 with dilatation of Bowman's capsules and proximal tubules, followed by pelvic dilatation and hydronephrosis. 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. Thus TAZ is essential for developmental mechanisms involved in kidney and lung organogenesis, whose disturbance may lead to the pathogenesis of common human diseases.
authors.affiliation: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Makita
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Uchijima
authors.forename: Koichi
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Amano
authors.forename: Qin
authors.initials: Q
authors.lastname: Chen
authors.forename: Takumi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Akihisa
authors.initials: A
authors.lastname: Mitani
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagawa
authors.forename: Erin V
authors.initials: EV
authors.lastname: Small
authors.forename: Patricia
authors.initials: P
authors.lastname: Cobo-Stark
authors.forename: Peter
authors.initials: P
authors.lastname: Igarashi
authors.forename: Masao
authors.initials: M
authors.lastname: Murakami
authors.forename: Junji
authors.initials: J
authors.lastname: Tominaga
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sato
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kurihara
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D048948:14-3-3 Proteins / Q000172:deficiency* / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007668:Kidney / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic / Q000378:metabolism*; D010641:Phenotype; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011141:Polyuria / Q000235:genetics / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators; D014867:Water / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D048868:Adaptor Proteins, Signal Transducing; D015534:Trans-Activators; C517794:Wwtr1 protein, mouse; D014867:Water