title: Mouse development is not obviously affected by the absence of dermatan sulfate epimerase 2 in spite of a modified brain dermatan sulfate composition.
abstract: Dermatan sulfate epimerase 2 (DS-epi2), together with its homolog DS-epi1, transform glucuronic acid into iduronic acid in DS polysaccharide chains. Iduronic acid gives DS increased chain flexibility and promotes protein binding. DS-epi2 is ubiquitously expressed and is the predominant epimerase in the brain. Here, we report the generation and initial characterization of DS-epi2 null mice. DS-epi2-deficient mice showed no anatomical, histological or morphological abnormalities. The body weights and lengths of mutated and wild-type littermates were indistinguishable. They were fertile and had a normal lifespan. Chondroitin sulfate (CS)/DS isolated from the newborn mutated mouse brains had a 38% reduction in iduronic acid compared with wild-type littermates, and compositional analysis revealed a decrease in 4-O-sulfate and an increase in 6-O-sulfate containing structures. Despite the reduction in iduronic acid, the adult DS-epi2-/- brain showed normal extracellular matrix features by immunohistological stainings. We conclude that DS-epi1 compensates in vivo for the loss of DS-epi2. These results extend previous findings of the functional redundancy of brain extracellular matrix components.
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bartolini
authors.forename: Martin A
authors.initials: MA
authors.lastname: Thelin
authors.forename: Uwe
authors.initials: U
authors.lastname: Rauch
authors.forename: Ricardo
authors.initials: R
authors.lastname: Feinstein
authors.forename: Ake
authors.initials: A
authors.lastname: Oldberg
authors.forename: Anders
authors.initials: A
authors.lastname: Malmström
authors.forename: Marco
authors.initials: M
authors.lastname: Maccarana
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology / Q000254:growth & development*; D002236:Carbohydrate Conformation; D002238:Carbohydrate Epimerases / Q000172:deficiency* / Q000235:genetics; D002478:Cells, Cultured; D003871:Dermatan Sulfate / Q000378:metabolism*; D004187:Disaccharides / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D055786:Gene Knockout Techniques; D007067:Iduronic Acid / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013431:Sulfates / Q000378:metabolism
chemical_list: D004187:Disaccharides; D013431:Sulfates; D003871:Dermatan Sulfate; D007067:Iduronic Acid; D002238:Carbohydrate Epimerases; C544542:dermatan sulfate epimerase 1, mouse