title: WISP3, the gene responsible for the human skeletal disease progressive pseudorheumatoid dysplasia, is not essential for skeletal function in mice.
abstract: In humans, loss-of-function mutations in WISP3 cause the autosomal recessive skeletal disease progressive pseudorheumatoid dysplasia (PPD) (Online Mendelian Inheritance in Man database number 208230). WISP3 encodes Wnt1-inducible signaling protein 3, a cysteine-rich, multidomain, secreted protein, whose paralogous CCN (connective tissue growth factor/cysteine-rich protein 61/nephroblastoma overexpressed) family members have been implicated in diverse biologic processes including skeletal, vascular, and neural development. To understand the role of WISP3 in the skeleton, we targeted the Wisp3 gene in mice by creating a mutant allele comparable to that which causes human disease. We also created transgenic mice that overexpress human WISP3 in cartilage. Surprisingly, homozygous Wisp3 mutant mice appear normal and do not recapitulate any of the morphological, radiographic, or histological abnormalities seen in patients with PPD. Mice that overexpress WISP3 are also normal. We conclude, that in contrast to humans, Wisp3 is not an essential participant during skeletal growth or homeostasis in mice.
authors.affiliation: Department of Genetics, Case Western Reserve University, 2109 Adelbert Road, BRB 719, Cleveland, OH 44106-4955, USA.
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Kutz
authors.forename: Yaoqin
authors.initials: Y
authors.lastname: Gong
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Warman
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001842:Bone and Bones / Q000378:metabolism*; D055511:CCN Intercellular Signaling Proteins; D002356:Cartilage / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018969:Insulin-Like Growth Factor Binding Proteins / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000502:physiology*; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D019076:Transgenes; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D055511:CCN Intercellular Signaling Proteins; C400081:CCN6 protein, human; D018076:DNA, Complementary; D018969:Insulin-Like Growth Factor Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D001616:beta-Galactosidase