NDLI: An inducible cartilage oligomeric matrix protein mouse model recapitulates human pseudoachondroplasia phenotype.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Posey, Karen L. Veerisetty, Alka C. Liu, Pieman Wang, Huiqiu R. Poindexter, Brian J. Bick, Roger Alcorn, Joseph L. Hecht, Jacqueline T.
Description	Country affiliation: United States Author Affiliation: Posey KL ( Department of Pediatrics, University of Texas Medical School, Houston, TX 77030, USA.)
Abstract	Cartilage oligomeric matrix protein (COMP) is a pentameric extracellular protein expressed in cartilage and other musculoskeletal tissues. Mutations in the COMP gene cause pseudoachondroplasia (PSACH), a severe dwarfing condition that has a growth plate chondrocyte pathology. PSACH is characterized by intracellular retention of COMP and other extracellular matrix (ECM) proteins, which form an ordered matrix within large rough endoplasmic reticulum cisternae. This accumulation is cytotoxic and causes premature chondrocyte cell death, thereby depleting chondrocytes needed for normal long bone growth. Research to define the underlying molecular mechanisms of PSACH has been hampered by the lack of a suitable model system. In this study, we achieved robust expression of human mutant (MT) or wild-type (WT) COMP in mice by using a tetracycline-inducible promoter. Normal growth plate distribution of ECM proteins was observed in 1-month-old WT-COMP and C57BL 6 control mice. In contrast, the structure of the MT-COMP growth plate recapitulated the findings of human PSACH growth plate morphology, including (1) retention of ECM proteins, (2) intracellular matrix formation in the rER cisternae, and (3) increased chondrocyte apoptosis. Therefore, we have generated the first mouse model to show extensive intracellular retention of ECM proteins recapitulating the human PSACH disease process at the cellular level.
File Format	HTM / HTML
ISSN	00029440
e-ISSN	15252191
DOI	10.2353/ajpath.2009.090184
Journal	The American Journal of Pathology
Issue Number	4
Volume Number	175
Language	English
Publisher	Elsevier (on behalf of the American Society for Investigative Pathology)
Publisher Date	2009-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Endoplasmic Reticulum Matrilin Proteins Osteochondrodysplasias Extracellular Matrix Proteins Protein Structure, Quaternary Genetics Disease Models, Animal Cartilage Oligomeric Matrix Protein Abnormalities Mice, Transgenic Discipline Pathology Glycoproteins Metabolism Collagen Type Ix Pathology Chemistry Phenotype Animals Growth Plate Chondrocytes Mice Mutation Apoptosis
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

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