SEQUENCE, STRUCTURE AND CHROMOSOMAL LOCALIZATION OF CRTM GENE ENCODING MOUSE CARTILAGE MATRIX PROTEIN AND ITS EXCLUSION AS A CANDIDATE FOR MURINE ACHONDROPLASIA

The mouse cartilage matrix protein gene (Crtm) was isolated from a cos mid library using a mouse Crtm cDNA fragment as probe. Crtm spans 12.2 kb from the start of translation to the polyadenylation signal sequen ce and comprises eight exons. Sequencing of the 1.9 kb 5' flanking reg ion revealed a TATA-like box 72 bp upstream from the initiator Met cod on as well as several cis-acting motifs known to bind eukaryotic trans cription factors. Analysis of the exon-intron junctions demonstrated t hat the last intron does not follow the gt/ag rule but belongs to the minor class of pre-mRNA introns that contain ''at'' and ''ac'' at thei r 5' and 3' ends, respectively. Single-strand conformation polymorphis m analysis was used to map Crtm to the distal part of chromosome 4 bet ween the microsatellite markers D4Mit16 and D4Mit339. Achodroplasia (c n), a recessive skeletal disorder in mice, has already been mapped to this region. Immunostaining for CMP and sequence of Crtm in cn/cn mice failed to reveal any disease-specific mutations, suggesting that muta tions in Crtm do not cause achondroplasia.