The Sagg /+ mouse is an ethylnitrosourea-derived mutant with a dermal phenotype similar to some of the subtypes of Ehlers–Danlos syndrome (EDS) and cutis laxa. The dermis of the Sagg /+ mouse has less dense and more disorganized collagen fibers compared to controls. The size of extracted Type I dermal collagen was the same as that observed in normal skin; however, more collagen could be extracted from Sagg /+ skin, which also showed decreased collagen content and decreased steady-state levels of α 1(I), α 2(I), α 1(V), and α 2(V) procollagen mRNAs. The biomechanical properties of Sagg /+ skin were significantly decreased relative to normal skin. However, there were no significant differences in the quantities of the major collagen cross-links, that is, dehydrohydroxylysinonorleucine and dehydrohistidinohydroxymerodesmosine between Sagg /+ and normal skin. Electron microscopic evaluation of Sagg /+ skin indicated that the mutation interferes with the proper formation of collagen fibrils and the data are consistent with a mutation in Type V collagen leading to haploinsufficiency with the formation of two sub-populations of collagen fibrils, one normal and one with irregular shape and a larger diameter. Further study of this novel mutation will allow the identification of new mechanisms involved in the regulation of normal and pathologic collagen gene expression.
