A disintegrin and metalloproteinase (ADAM) represents a protein family possessing both metalloproteinase and disintegrin domains. ADAMTS-1, an ADAM family member cloned from cachexigenic colon adenocarcinoma, is unusual in that it contains thrombospondin type I motifs and anchors to the extracellular matrix. To elucidate the biological role of ADAMTS-1, we developed ADAMTS-1–null mice by gene targeting. Targeted disruption of the mouse ADAMTS-1 gene resulted in growth retardation with adipose tissue malformation. Impaired female fertilization accompanied by histological changes in the uterus and ovaries also resulted. Furthermore, ADAMTS-1–/– mice demonstrated enlarged renal calices with fibrotic changes from the ureteropelvic junction through the ureter, and abnormal adrenal medullary architecture without capillary formation. ADAMTS-1 thus appears necessary for normal growth, fertility, and organ morphology and function. Moreover, the resemblance of the renal phenotype to human ureteropelvic junction obstruction may provide a clue to the pathogenesis of this common congenital disease.
Takayuki Shindo, Hiroki Kurihara, Kouji Kuno, Hitoshi Yokoyama, Takashi Wada, Yukiko Kurihara, Tomihiko Imai, Yuhui Wang, Masafumi Ogata, Hiroaki Nishimatsu, Nobuo Moriyama, Yoshio Oh-hashi, Hiroyuki Morita, Takatoshi Ishikawa, Ryozo Nagai, Yoshio Yazaki, Kouji Matsushima