title: Dermatan sulfate epimerase 1 deficient mice as a model for human abdominal wall defects.
abstract: BACKGROUND
  Dermatan sulfate (DS) is a highly sulfated polysaccharide with a variety of biological functions in extracellular matrix organization and processes such as tumorigenesis and wound healing. A distinct feature of DS is the presence of iduronic acid, produced by the two enzymes, DS-epimerase 1 and 2, which are encoded by Dse and Dsel, respectively.
  
  
  METHODS
  We have previously shown that Dse knockout (KO) mice in a mixed C57BL/6-129/SvJ background have an altered collagen matrix structure in skin. In the current work we studied Dse KO mice in a pure NFR genetic background.
  
  
  RESULTS
  Dse KO embryos and newborns had kinked tails and histological staining revealed significantly thicker epidermal layers in Dse KO mice when compared with heterozygote (Het) or wild-type (WT) littermates. Immunochemical analysis of the epidermal layers in newborn pups showed increased expression of keratin 5 in the basal layer and keratin 1 in the spinous layer. In addition, we observed an abdominal wall defect with herniated intestines in 16% of the Dse KO embryos. Other, less frequent, developmental defects were exencephaly and spina bifida.
  
  
  CONCLUSIONS
  We conclude that the combination of defective collagen structure in the dermis and imbalanced keratinocyte maturation could be responsible for the observed developmental defects in Dse KO mice. In addition, we propose that Dse KO mice could be used as a model in pathogenetic studies of human fetal abdominal wall defects.
authors.affiliation: Department of Experimental Medical Science, BMC D10, Lund University, Lund, Sweden.
authors.forename: Renata
authors.initials: R
authors.lastname: Gustafsson
authors.forename: Xanthi
authors.initials: X
authors.lastname: Stachtea
authors.forename: Marco
authors.initials: M
authors.lastname: Maccarana
authors.forename: Emma
authors.initials: E
authors.lastname: Grottling
authors.forename: Erik
authors.initials: E
authors.lastname: Eklund
authors.forename: Anders
authors.initials: A
authors.lastname: Malmström
authors.forename: Ake
authors.initials: A
authors.lastname: Oldberg
mesh_terms: D034861:Abdominal Wall / Q000002:abnormalities*; D000818:Animals; D002238:Carbohydrate Epimerases / Q000172:deficiency / Q000235:genetics*; D003871:Dermatan Sulfate / Q000378:metabolism; D020405:Dermis / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D015870:Gene Expression; D046449:Hernia, Abdominal / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053556:Keratin-1 / Q000235:genetics / Q000378:metabolism; D053569:Keratin-15 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009436:Neural Tube Defects / Q000150:complications / Q000235:genetics / Q000473:pathology; D016135:Spinal Dysraphism / Q000150:complications / Q000235:genetics / Q000473:pathology
chemical_list: D053556:Keratin-1; D053569:Keratin-15; C492053:Krt15 protein, mouse; D003871:Dermatan Sulfate; D002238:Carbohydrate Epimerases; C544542:dermatan sulfate epimerase 1, mouse
keywords: abdominal wall defect; dermatan sulfate epimerase 1; embryonic development; epidermis; neural tube defects