Transgenic mice with inactive alleles for procollagen N-proteinase (ADAMTS-2) develop fragile skin and male sterility

Transgenic mice were prepared with inactive alleles for procollagen N-prote inase (ADAMTS-2, where ADAMTS stands for a disintegrin and metalloproteinas e with thrombospondin repeats). Homozygous mice were grossly normal at birt h, but after 1-2 months they developed thin skin that tore after gentle han dling. Although the gene was inactivated, a large fraction of the N-propept ides of type I procollagen in skin and the N-propeptides of type II procoll agen 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 collag en fibrils in newborn mice. However, in two-month-old mice. the collagen fi brils in skin were seen as bizarre curls in cross-section and the mean diam eters 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 microscop y or by polarized-light microscopy. Female homozygous mice were fertile, bu t male mice were sterile with a marked decrease in testicular sperm. Theref ore the results indicated that ADAMTS-2 plays an essential role in the matu ration of spermatogonia.