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

Ryosuke Makita, Yasunobu Uchijima, Koichi Nishiyama, Tomokazu Amano, Qin Chen, Takumi Takeuchi, Akihisa Mitani, Takahide Nagase, Yutaka Yatomi, Hiroyuki Aburatani, Osamu Nakagawa, Erin V. Small, Patricia Cobo-Stark, Peter Igarashi, Masao Murakami, Junji Tominaga, Takahiro Sato, Tomoichiro Asano, Yukiko Kurihara, Hiroki Kurihara

Research output: Contribution to journalArticle

162 Citations (Scopus)

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume294
Issue number3
DOIs
StatePublished - Mar 2008

Fingerprint

Homozygote
Cysts
Kidney
Lung
Dilatation
Multicystic Dysplastic Kidney
Bowman Capsule
PDZ Domains
Polyuria
Polycystic Kidney Diseases
Pulmonary Emphysema
Organogenesis
Hydronephrosis
Gene Silencing
Proteins
Transcription Factors
Parturition
Membranes

Keywords

  • Knockout mice
  • Renal disease
  • Transcription factor

ASJC Scopus subject areas

  • Physiology

Cite this

Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ. / Makita, Ryosuke; Uchijima, Yasunobu; Nishiyama, Koichi; Amano, Tomokazu; Chen, Qin; Takeuchi, Takumi; Mitani, Akihisa; Nagase, Takahide; Yatomi, Yutaka; Aburatani, Hiroyuki; Nakagawa, Osamu; Small, Erin V.; Cobo-Stark, Patricia; Igarashi, Peter; Murakami, Masao; Tominaga, Junji; Sato, Takahiro; Asano, Tomoichiro; Kurihara, Yukiko; Kurihara, Hiroki.

In: American Journal of Physiology - Renal Physiology, Vol. 294, No. 3, 03.2008.

Research output: Contribution to journalArticle

Makita, R, Uchijima, Y, Nishiyama, K, Amano, T, Chen, Q, Takeuchi, T, Mitani, A, Nagase, T, Yatomi, Y, Aburatani, H, Nakagawa, O, Small, EV, Cobo-Stark, P, Igarashi, P, Murakami, M, Tominaga, J, Sato, T, Asano, T, Kurihara, Y & Kurihara, H 2008, 'Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ', American Journal of Physiology - Renal Physiology, vol. 294, no. 3. https://doi.org/10.1152/ajprenal.00201.2007
Makita, Ryosuke ; Uchijima, Yasunobu ; Nishiyama, Koichi ; Amano, Tomokazu ; Chen, Qin ; Takeuchi, Takumi ; Mitani, Akihisa ; Nagase, Takahide ; Yatomi, Yutaka ; Aburatani, Hiroyuki ; Nakagawa, Osamu ; Small, Erin V. ; Cobo-Stark, Patricia ; Igarashi, Peter ; Murakami, Masao ; Tominaga, Junji ; Sato, Takahiro ; Asano, Tomoichiro ; Kurihara, Yukiko ; Kurihara, Hiroki. / Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ. In: American Journal of Physiology - Renal Physiology. 2008 ; Vol. 294, No. 3.
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