Complete exon-intron organization and chromosomal location of the gene formouse type XIII collagen (col13a1) and comparison with its human homologue

Recent findings indicate that type XIII collagen is a transmembrane protein with a short N-terminal sytocsolic domain, a single transmembrane domain a nd a large, mainly collagenous ectodomain. The complete exon-intron structu re of the gene coding for the mouse alpha 1(XIII) collagen chain, coll3a1, has now been characterized from genomic clones spanning over 180 kilobases (kb) and shown to be approximately 135 kb in size and to contain 42 exons v arying between 8 base pairs (bp), the shortest exon in the genes encoding t he various collagens, and 836 bp. Nuclease S1 mapping and 5'RACE resulted i n identification of multiple transcription initiation points in the mouse g ene, ranging between 470 and 548 bp upstream from the initiation methionine . This is in good agreement with a recently identified human EST clone exte nding 537 bp upstream from the initiation methionine. The 836-bp first exon of the mouse gene covers both the long 5' untranslated region and also a 3 6-residue cytosolic portion, a 23-residue transmembrane domain, and 37 resi dues of the 60-residue non-collagenous ectodomain immediately adjacent to t he plasma membrane. One striking feature of the exons encoding solely colla genous sequences is the abundance of 27-bp exons, half the ancestral 54-bp size characteristic of fibrillar collagen genes, while the others vary betw een 8 and 144 bp, including instances of 36-, 45- and 54-bp exons. Determin ation of approximately 2.6 kb of sequences upstream of the initiation methi onine of both the mouse and human genes and the identification of a clone c ontaining four exons and spanning a gap in the previously characterized hum an clones allowed detailed comparison of the two genes. The exon-intron str uctures were found to be completely conserved between the species, and both genes have their 5' untranslated region preceded by a highly homologous ap parent promoter region of approximately 350 bp containing a modified TATAA motif and several GC boxes. The chromosomal location of the mouse gene was determined by SSCP and fluorescence in situ hybridization and found to be a t chromosome 10, band 4, between markers D10Mit5 - 2.3 +/- 1.6 cM - coll3a1 - 3.4 +/- 1.9 cM - D10Mit15. This result indicates that the mouse type XII I collagen gene and its human counterpart are located in chromosomal segmen ts with conserved syntenies (The GenBank accession numbers for the mouse ge ne are AF063666-AF063693. The new GenBank accession number for the 5' end o f the human type XIII collagen gene is AF071009). (C) 1999 Elsevier Science B.V./International Society of Matrix Biology. All rights reserved.