Transgenic mice with inactive alleles for procollagen N-proteinase (ADAMTS-2) develop fragile skin and male sterility.
Transgenic mice with inactive alleles for procollagen N-proteinase (ADAMTS-2) develop fragile skin and male sterility.
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DOI：
10.1042/bj3550271
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发表时间：
2001-04
期刊：
影响因子：
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通讯作者：
Shi-wu Li;M. Arita;A. Fertala;Y. Bao;G. Kopen;Teemu K. Långsjö;M. Hyttinen;H. Helminen;D. Prockop
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文献类型：
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作者：
Shi-wu Li;M. Arita;A. Fertala;Y. Bao;G. Kopen;Teemu K. Långsjö;M. Hyttinen;H. Helminen;D. Prockop
制备具有前胶原N-蛋白酶（ADAMTS-2;其中ADAMTS代表具有血小板反应蛋白重复序列的去整合素和金属蛋白酶）的失活等位基因的转基因小鼠。纯合子小鼠在出生时大体正常，但1-2个月后，它们的皮肤变薄，在轻轻处理后会撕裂。虽然该基因被灭活，但皮肤中I型前胶原的大部分N-前肽和软骨中II型前胶原的大部分N-前肽被切割。因此，研究结果表明，这些组织含有一种或多种额外的酶，可以缓慢地处理蛋白质。电子显微镜检查未发现新生小鼠胶原纤维形态的任何缺陷。然而，在两个月大的小鼠中，皮肤中的胶原原纤维在横截面上被观察到为奇异的卷曲，并且原纤维的平均直径约为1.5 μ m。一半的控制。虽然软骨中II型前胶原的N-前肽的一部分没有被切割，但通过电子显微镜或偏振光显微镜观察到原纤维的形态没有缺陷。雌性纯合子小鼠是可生育的，但雄性小鼠是不育的，睾丸精子明显减少。说明ADAMTS-2在精原细胞成熟过程中起重要作用。
Transgenic mice were prepared with inactive alleles for procollagen N-proteinase (ADAMTS-2; where ADAMTS stands for a disintegrin and metalloproteinase with thrombospondin repeats). Homozygous mice were grossly normal at birth, but after 1-2 months they developed thin skin that tore after gentle handling. Although the gene was inactivated, a large fraction of the N-propeptides of type I procollagen in skin and the N-propeptides of type II procollagen in cartilage were cleaved. Therefore the results suggested the tissues contained one or more additional enzymes that slowly process the proteins. Electron microscopy did not reveal any defects in the morphology of collagen fibrils in newborn mice. However, in two-month-old mice, the collagen fibrils in skin were seen as bizarre curls in cross-section and the mean diameters of the fibrils were approx. half of the controls. Although a portion of the N-propeptides of type II procollagen in cartilage were not cleaved, no defects in the morphology of the fibrils were seen by electron microscopy or by polarized-light microscopy. Female homozygous mice were fertile, but male mice were sterile with a marked decrease in testicular sperm. Therefore the results indicated that ADAMTS-2 plays an essential role in the maturation of spermatogonia.