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


METHODS
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.


RESULTS
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.


CONCLUSIONS
The human COL2A1 gene with the Arg519Cys mutation causes osteochondrodysplasia in mice, as it does in humans.
Sahlman
Janne
J
Seinäjoki Central Hospital, Seinäjoki, Finland.
Pitkänen
Marja T
MT
Prockop
Darwin J
DJ
Arita
Machiko
M
Li
Shi-Wu
SW
Helminen
Heikki J
HJ
Långsjö
Teemu K
TK
Puustjärvi
Kaija
K
Lammi
Mikko J
MJ
D000483:Alleles; D000818:Animals; D024043:Collagen Type II / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D011859:Radiography
C447413:Col2a1 protein, mouse; D024043:Collagen Type II