These targeted mutant mice carry a knockout allele of the Matn1 gene (matrilin 1, cartilage matrix protein). Cartilage shows abnormal type II collagen fibrillogenesis and fibril organization.
Qian Chen, Rhode Island Hospital, Brown University
Matrilin-1 (cartilage matrix protein; Matn1) is a homotrimeric protein that forms collagen-dependent and collagen-independent fibrils in the extracelluar matrix of cartilage.
These targeted mutant mice carry a knockout allele of the Matn1 gene. Ultrastructural studies of the cartilage of long bone growth plates from homozygotes reveals an abnormal type II collagen fibrillogenesis and fibril organization in the matrix of the zone of maturation. In contrast to the meshwork-like organization of collagen fibrils in wildtype cartilage, the fibrils of matrilin null animals are unidirectional. Fibrils in the mutant cartilage also become significantly larger in diameter than those of controls. The cartilage matrix is stiffer in knockout mice, and the knee joint is prone to injury-induced osteoarthritis.
Reduced matrilin content in the pericellular matrix surrounding chondrocytes decreases their proliferative/gene expression responses to mechanical stimulation. Chondrocytes from the knockout mice cultured under mechanical pressure show only a 0.5-fold increase in mRNA levels of collagen type X, in comparison to the more than 2.5-fold increase seen in wildtype chondrocytes.
Mice heterozygous or homozygous for the targeted allele grow normally and display no major phenotypic differences from the wild-type littermates during skeletal development. Homozygous null mice are fully viable with normal fecundity.
A 1.8 kbp PGK-neo fragment replacing 0.8 kbp of genomic sequence encoding exon 4 and a portion of exon 5 was introduced to 129S4/SvJae-derived J1 embryonic stem (ES) cells by homologous recombination. Targeted ES cells were microinjected into C57BL/6 blastocysts. The resulting chimeric male mice were bred to C57BL/6 females. This strain was maintained on a mixed C57BL/6-129 genetic background prior to sending to The Jackson Laboratory Repository. Upon arrival, sperm was cryopreserved. To generate the living colony, an aliquot of the frozen sperm was used to fertilize oocytes from B6129SF1/J female mice (Stock No. 101043). The mutant mice were then bred together, to wildtype mice from the colony, or to B6129SF1/J mice.
|Allele Name||targeted mutation 1, Paul F Goetinck|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Paul F Goetinck; Matn1tm1Goe|
|Gene Symbol and Name||Matn1, matrilin 1, cartilage matrix protein|
|Gene Synonym(s)||Mat1; cartiliage matrix protein; CRTM; CMP; matrilin-1; Crtm; Crtm|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin cassette replaced exon 4 and part of exon 5. In situ hybridization and immunohistochemical analysis in distal growth plates of E15 homozygous embryos demonstrated an absence of transcript and protein.|
Homozygotes and heterozygotes are viable and fertile.
When using the B6;129S-Matn1tm1Goe/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #024003 in your Materials and Methods section.
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