Molecular characterization and chromosomal assignment of equine cartilage derived retinoic acid sensitive protein (CD-RAP)/melanoma inhibitory activity (MIA).
Abstract: Cartilage-derived retinoic acid sensitive protein (CD-RAP) also known as melanoma inhibitory activity (MIA) has already been established as a marker for chondrocyte differentiation and a number of cancerous conditions in humans. Studies have also shown that CD-RAP/MIA is a potential marker of joint disease. The objective of this study was to characterize the equine CD-RAP/MIA gene and thus make it available as a marker in cartilage research and clinical studies. Gene analysis revealed that the equine gene (GenBank accession no. EF679787) consists of four exons and three introns, and the homology to the human gene is 90% for the translated region. The upstream sequence includes regulatory elements and putative transcription factor binding sites previously described in the human and murine promoter regions. The deduced amino acid sequence consists of 130 aa including a signal peptide of 23 aa, and has a 91% identity to the human protein. Using radiation hybrid mapping, the CD-RAP/MIA gene was localized to the p arm of equine chromosome 10 (ECA10p), which is in accordance with prediction based on the current human-equine comparative map. Gene expression studies showed expression of CD-RAP/MIA mRNA in articular cartilage and chondrocytes from horses with no signs of joint disease. The expression decreased as the cells dedifferentiated in monolayer culture. We also identified an equine CD-RAP/MIA splice variant similar to that reported in humans. The CD-RAP/MIA protein was detected in equine synovial fluid, serum and culture medium from chondrocyte cultures. In conclusion, CD-RAP/MIA is expressed in equine cartilage and chondrocytes, and the protein can be detected in equine serum, synovial fluid and in culture medium from chondrocyte cultures. The equine gene and resulting protein share great homology with the human gene, making future studies on CD-RAP/MIAs potential as a marker in joint disease possible using the equine joint as a model.
Publication Date: 2007-10-05 PubMed ID: 17977671DOI: 10.1016/j.gene.2007.09.022Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research article investigates the gene responsible for producing Cartilage-Derived Retinoic Acid Sensitive Protein (CD-RAP) or Melanoma Inhibitory Activity (MIA) in horses. It confirms that this gene shares a high degree of similarity with its human counterpart, suggesting it could be used as a marker in research into joint diseases.
Research Objectives and Methods
- The aim of this study was to map out the equine version of the gene CD-RAP/MIA, already known to be a significant marker in human cartilage differentiation and some types of cancer. By doing so, it could be used in research related to joint disease, since it’s been identified as a potential marker for such conditions.
- The method involved gene analysis, which showed that the horse version of the gene consists of four “exons” and three “introns”, with translation segments showing a 90% similarity to the human gene.
Research Findings
- As a result of the study, a similarity of 91% was found between the deduced amino acid sequence of horses and humans.
- The gene CD-RAP/MIA was localised to a specific section of the horse’s 10th chromosome, matching predictions from existing comparative maps of human and horse genes.
- The team also detected the CD-RAP/MIA protein in horse joint fluid, serum, and in a culture medium from isolated cartilage cells.
Expression and Variants
- The research confirmed the expression of CD-RAP/MIA mRNA in healthy horse cartilage and chondrocytes, although this expression decreases as the cells lose their differentiation in a single-layered culture.
- Researchers identified a variant of the CD-RAP/MIA protein in horses, similar to one previously found in humans.
Conclusion and Significance
- The research concludes that CD-RAP/MIA is expressed in equine cartilage and chondrocytes, indicating a significant homology with human gene expression.
- Given the similarity between human and equine CD-RAP/MIA genes and proteins, it is proposed that future research could use the equine joint as a model for studying the potential of CD-RAP/MIA as a marker for joint disease.
Cite This Article
APA
Berg LC, Mata X, Thomsen PD.
(2007).
Molecular characterization and chromosomal assignment of equine cartilage derived retinoic acid sensitive protein (CD-RAP)/melanoma inhibitory activity (MIA).
Gene, 407(1-2), 98-104.
https://doi.org/10.1016/j.gene.2007.09.022 Publication
Researcher Affiliations
- Faculty of Life Sciences, Department of Animal and Veterinary Basic Sciences, University of Copenhagen, Groennegaardsvej 7, Frederiksberg C, Copenhagen, Denmark. lcb@life.ku.dk
MeSH Terms
- Animals
- Base Sequence
- Cartilage / metabolism
- Chromosome Mapping
- Chromosomes / genetics
- Exons
- Extracellular Matrix Proteins / blood
- Extracellular Matrix Proteins / genetics
- Gene Expression
- Horses / genetics
- Introns
- Molecular Sequence Data
- Promoter Regions, Genetic
- RNA Splicing
- Tretinoin / metabolism
Citations
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