Collagen dysregulation in the dermis of the Sagg/+ mouse: a loose skin model.
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 alpha1(I), alpha2(I), alpha1(V), and alpha2(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.
Christner
Paul J
PJ
Department of Medicine, The Division of Rheumatology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541, USA. paul.christner@jefferson.edu
Gentiletti
Julieta
J
Peters
Josephine
J
Ball
Simon T
ST
Yamauchi
Mitsuo
M
Atsawasuwan
Phimon
P
Beason
David P
DP
Soslowsky
Louis J
LJ
Birk
David E
DE
D000818:Animals; D002874:Chromosome Mapping; D003094:Collagen / Q000032:analysis / Q000235:genetics*; D003483:Cutis Laxa / Q000209:etiology* / Q000235:genetics; D004195:Disease Models, Animal; D004535:Ehlers-Danlos Syndrome / Q000209:etiology* / Q000235:genetics; D005038:Ethylnitrosourea / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D013718:Tensile Strength
D012333:RNA, Messenger; D003094:Collagen; D005038:Ethylnitrosourea