Cloning of mouse type VII collagen reveals evolutionary conservation of functional protein domains and genomic organization.
Type VII collagen is the major component of anchoring fibrils, attachment structures necessary for stable association of the dermal-epidermal basement membrane to the underlying dermis. The critical role of the anchoring fibrils in providing integrity to the cutaneous basement membrane zone is attested to by demonstration of mutations in the type VII collagen gene (COL7A1) in patients with dystrophic epidermolysis bullosa. To gain insight into the evolutionary conservation of the type VII collagen gene, in this study we have cloned the entire mouse type VII collagen cDNA and elucidated the intron-exon organization of the corresponding gene, Col7a1. The coding region of the cDNA consists of 8832 nucleotides encoding a polypeptide of 2944 amino acids with a calculated molecular mass of approximately 295 kDa. Computer analysis predicted the presence of an 18-amino acid signal peptide. Comparison of the deduced mouse alpha1(VII) collagen polypeptide with the corresponding human sequence indicated 84.7% identity and 90.4% homology at the amino acid level. In addition, the domain organization, including imperfections and interruptions within the collagenous domain consisting of Gly-X-Y repeat sequences, was highly conserved. The unit of evolutionary period between the full-length human and mouse polypeptides was calculated to be 6.5 million years, however, suggesting relatively rapid evolutionary divergence in comparison to other collagen genes. Elucidation of the intron-exon organization of the mouse Col7a1 gene revealed 118 distinct exons, the same number as present in the human gene. These data indicate a high degree of structural conservation between the human and mouse type VII collagen, supporting the critical role of this collagen as the major component of the anchoring fibrils.
Kivirikko
S
S
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Li
K
K
Christiano
A M
AM
Uitto
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D003001:Cloning, Molecular; D003094:Collagen / Q000235:genetics*; D017124:Conserved Sequence; D006224:Cricetinae; D016678:Genome; D006801:Humans; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data
D003094:Collagen