Mouse cartilage matrix deficiency (cmd) is an autosomal recessive mutation characterized by cleft palate, short limbs, tail and snout. Heterozygous mice show normal size and phenotype, while homozygous mice die just after birth due to respiratory failure. Biochemical and immunohistochemical characterization of cmd cartilage reveals normal levels of type II collagen and link protein, but an absence of the large cartilage proteoglycan, aggrecan. Here, we have mapped the aggrecan gene to a region of mouse chromosome 7 near the cmd locus. DNA sequencing of the aggrecan gene identified a 7 bp deletion in exon 5 resulting in a severely truncated molecule. The finding of an aggrecan mutation in the cmd mouse confirms the critical role of aggrecan in cartilage formation.
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Watanabe, H., Kimata, K., Line, S. et al. Mouse cartilage matrix deficiency (cmd) caused by a 7 bp deletion in the aggrecan gene. Nat Genet 7, 154–157 (1994). https://doi.org/10.1038/ng0694-154
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