ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function.
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.
Shindo
T
T
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Kurihara
H
H
Kuno
K
K
Yokoyama
H
H
Wada
T
T
Kurihara
Y
Y
Imai
T
T
Wang
Y
Y
Ogata
M
M
Nishimatsu
H
H
Moriyama
N
N
Oh-hashi
Y
Y
Morita
H
H
Ishikawa
T
T
Nagai
R
R
Yazaki
Y
Y
Matsushima
K
K
D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D000311:Adrenal Glands / Q000002:abnormalities; D000818:Animals; D019483:Disintegrins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology*; D006128:Growth / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007247:Infertility, Female / Q000209:etiology; D007668:Kidney / Q000002:abnormalities; D008297:Male; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010053:Ovary / Q000002:abnormalities; D010641:Phenotype; D011247:Pregnancy; D014599:Uterus / Q000002:abnormalities
D019483:Disintegrins; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; C486323:Adamts1 protein, mouse; D008666:Metalloendopeptidases