title: A mutation of the Col2a1 gene (G1170S) alters the transgenic murine phenotype and cartilage matrix homeostasis.
abstract: OBJECTIVE
  Genomic studies have revealed that there is a significant association between a point mutation of the human Col2A1 gene (G1170S) and several hip disorders. The purpose of the study was to explore the phenotype and altered cartilage matrix homeostasis of transgenic mice carrying this mutated Col2a1 gene.
  
  
  METHODS
  Wild-type and transgenic mice were used as the control and study groups, respectively. Body weight measurement, radiographic analysis, and histological analysis of the mice were carried out to describe differences between the wild-type and transgenic mice at different ages. Cartilage metabolism studies were also carried out, including an MTT assay of cellular proliferation and nitric oxide and glycosaminoglycan assays. Allelic expression levels of the mutant A allele and the normal G allele were established by TaqMan assay. Cytokine and protease gene expression were measured.
  
  
  RESULTS
  Transgenic mice had a lower mean body weight, a deformed skeletal structure, and abnormal cartilage histomorphology. Chondrocyte proliferation was significantly compromised and this was linked to significantly higher NO secretion and less soluble glycosaminoglycan formation. TNF-α and IL-1β gene expression was significantly upregulated, while MMP-13 gene expression was significantly downregulated.
  
  
  CONCLUSIONS
  The mutant G1170S Col2a1 gene in mice clearly alters the transgenic murine phenotype and cartilage matrix homeostasis.
authors.affiliation: Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Orthopedic Surgery, Taipei City Hospital Zhongxing Branch, Taipei, Taiwan, ROC.
authors.forename: Ruei-Cheng
authors.initials: RC
authors.lastname: Yang
authors.affiliation: Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu City, Taiwan, ROC.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, Taipei, Taiwan, ROC; Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Ching-Yun
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan, ROC; Genome Research Center, National Yang-Ming University, Taipei, Taiwan, ROC; Division of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan, ROC.
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, ROC. Electronic address: ckcheng2009@gmail.com.
authors.forename: Cheng-Kung
authors.initials: CK
authors.lastname: Cheng
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC; Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC; Department of Orthopedic Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu City, Taiwan, ROC. Electronic address: drjssun@gmail.com.
authors.forename: Jui-Sheng
authors.initials: JS
authors.lastname: Sun
mesh_terms: D000483:Alleles; D000818:Animals; D002356:Cartilage / Q000473:pathology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology; D024043:Collagen Type II / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006706:Homeostasis; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype
chemical_list: C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D016207:Cytokines; D009569:Nitric Oxide; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse
keywords: Col2a1; cartilage; homeostasis; phenotype; transgenic mice