An inbred line of transgenic mice expressing an internally deleted gene for type II procollagen (COL2A1). Young mice have a variable phenotype of a chondrodysplasia and older mice have osteoarthritic changes in joints.

Abstract

Studies were carried out on a line of transgenic mice that expressed an internally deleted COL2A1 gene and developed a phenotype resembling human chondrodysplasias (Vandenberg et al. 1991. Proc. NatL. Acad. Sci. USA. 88:7640-7644. Marked differences in phenotype were observed with propagation of the mutated gene in an inbred strain of mice in that -15% of the transgenic mice had a cleft palate and a lethal phenotype, whereas the remaining mice were difficult to distinguish from normal littermates. 1-d-and 3-mo-old transgenic mice that were viable showed microscopic signs of chondrodysplasia with reduced amounts of collagen fibrils in the cartilage matrix, dilatation of the rough surfaced endoplasmic reticulum in the chondrocytes, and decrease of optical path difference in polarized light microscopy. The transgenic mice also showed signs of disturbed growth as evidenced by lower body weight, lower length and weight of the femur, decreased bone collagen, decreased bone mineral, and decreased resistance of bone to breakage. Comparisons of mice ranging in age from 1 d to 15 mo demonstrated that there was decreasing evidence of a chondrodysplasia as the mice grew older. Instead, the most striking feature in the 15-mo-old mice were degenerative changes of articular cartilage similar to osteoarthritis. (J. Clin. Invest. 1993. 92:582-595.)

Inactivation of one allele of the type II collagen gene alters the collagen network in murine articular cartilage and makes cartilage softer

“…This heterozygous knockout reduced the synthesis levels of pro-α1(II) chains to about half the normal level,25 but no gross disease developed in cartilaginous tissues 24. The genotype of newborn mice was verified by a polymerase chain reaction as earlier described 26.…”

Animal Models for Cartilage Regeneration and Repair

“…Transgenic animals are used to study the effects of a particular gene or protein on cartilage repair and regeneration. [23][24][25][26][27][28] For example, in the MRL=MpJ (JAX Ò , Jackson Laboratories, Bar Harbor, ME) mouse strain, the cartilage defects healed better than similar defects in C57Bl=6 mice. This was postulated to result from lower circulating levels of the proinflammatory cytokine interleukin 1a and higher levels of antiinflammatory cytokines in MRL=MpJ ( JAX) mice compared to their wild-type counterparts.…”

Osteoarthritis: New Insights in Animal Models

“…Transgenic mice whit defect in type II collagen show mild chondrodysplasia phenotype and OA [51, 52], transgenic mice whit defect I type IX collagens show OA and mild chondrodysplasia with ocular involvement [53]. Involvement of matrix metalloproteinases, especially MMP-13, has been demonstrated in the degradation of cartilage and the development of human OA lesions [54].…”