Dermatan sulfate epimerase 1 deficient mice as a model for human abdominal wall defects. Issue 9 (4th September 2014)

• Record Type: Journal Article
• Authors: Gustafsson, Renata; Stachtea, Xanthi; Maccarana, Marco; Grottling, Emma; Eklund, Erik; Malmström, Anders; Oldberg, Åke
• Is Part Of: Birth defects research. Volume 100:Issue 9(2014:Sep.)
• Page Start: 712
• Page End: 720
• Publication Date: 2014-09-04
• Subjects: Teratology -- Periodicals; Abnormalities, Human -- Research -- Periodicals; Abnormalities, Human -- Periodicals; 616.043
• DOI: 10.1002/bdra.23300
• Languages: English
• ISSNs: 1542-0752

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bdra23300-sec-0001" sec-type="section"> <title>Background</title> <p>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 <italic>Dse</italic> and <italic>Dsel</italic>, respectively.</p> </sec> <sec id="bdra23300-sec-0002" sec-type="section"> <title>Methods</title> <p>We have previously shown that <italic>Dse</italic> 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 <italic>Dse</italic> KO mice in a pure NFR genetic background.</p> </sec> <sec id="bdra23300-sec-0003" sec-type="section"> <title>Results</title> <p> <italic>Dse</italic> KO embryos and newborns had kinked tails and histological staining revealed significantly thicker epidermal layers in <italic>Dse</italic> 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 <italic>Dse</italic> KO embryos. Other, less frequent, developmental defects were exencephaly and spina bifida.</p> </sec> <sec id="bdra23300-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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 <italic>Dse</italic> KO mice. In addition, we propose that <italic>Dse</italic> KO mice could be used as a model in pathogenetic studies of human fetal abdominal wall defects. Birth Defects Research (Part A) 100:712–720, 2014. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>