A human COL2A1 gene with an Arg519Cys mutation causes osteochondrodysplasia in transgenic mice

Seinäjoki Central Hospital, Seinäjoki, Finland.
Arthritis & Rheumatology (Impact Factor: 7.76). 11/2004; 50(10):3153-60. DOI: 10.1002/art.20552
Source: PubMed


An arginine-to-cysteine substitution at position 519 of the COL2A1 gene causes early generalized osteoarthritis with mild chondrodysplasia in humans. In this study, a human COL2A1 gene with the same mutation was introduced into a murine genome having 1 or no alleles of the murine Col2a1 gene, and the skeletal phenotypes of the transgenic mice were compared with those of control mice.
Mice with 1 allele of the normal murine Col2a1 gene and 1 allele of the mutated human COL2A1 gene (n = 10), those with no murine Col2a1 gene and 2 alleles of the mutated human COL2A1 gene (n = 13), those with no murine Col2a1 gene and only 1 allele of the mutated COL2A1 gene (n = 9), and normal control mice (n = 11) were studied for skeletal abnormalities, using radiographic imaging and light microscopic analyses of histologic sections. The collagen network of cartilage was also investigated with transmission electron microscopy.
At 2 months of age, all transgenic mice had dysplastic changes in their long bones, flattened vertebral bodies, and osteoarthritic changes in their joints. The intervertebral discs of the transgenic animals were degenerated, and their histologic structure was disturbed. The changes were more severe in mice with no murine Col2a1 allele.
The human COL2A1 gene with the Arg519Cys mutation causes osteochondrodysplasia in mice, as it does in humans.

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Available from: Heikki Juhani Helminen, Oct 13, 2014
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    • "To study the COL2A1 mutation phenotype and the possible mechanisms behind it, at least 13 different mouse models have been reported (see Table S1) [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27]. Most transgenic mice have a phenotype of chondrodysplasia/spondyloepiphyseal dysplasia, with nonfatal malformations in heterozygotes, and lethal deformities in homozygotes. "
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    • "In the past few years, genetic links to OA have been established, and the first mutations in the collagen type II gene involved in the disease described [2,3]. More recently, other genes associated with the WNT and GDF signalling pathways have been implicated in OA susceptibility [4-6]. "
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    ABSTRACT: Diss. -- Oulun yliopisto.
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