Structure and expression of the C3 gene

Abstract

To map the multiple interactive sites on the C3 polypeptide, it is advantageous to combine the approaches of protein chemistry, nucleic acid technology, and molecular biology. This review summarizes the currently known molecular properties of mouse liver C3 mRNA, cloned C3 cDNA, and genomic DNA. Original data communicated have specified the amino acid sequence of the 215 amino-terminal residues of mature mouse C3 beta. Southern blot analysis of liver DNA indicated that the mouse genome contains only one type of C3 gene, that murine and human C3 sequences strongly cross-hybridize, and that the human C3 gene is not somatically rearranged. Included are descriptions of the first human C3 genomic DNA clones, their preparation, and their use to map the human C3 gene to chromosome 19 in linkage with the myotonic dystrophy (DM) locus. After a brief survey of reports describing inherited human C3 deficiencies, we discuss a Dutch family and their three members with total homozygous C3 deficiency who were the subjects of a recent publication. The restricted synthesis of C3 in major and minor producer tissues is discussed and it is proposed that the C3 gene provides a good model system for studying the molecular basis of tissue-specific gene expression. Data are presented documenting the production of C3 in two established mouse macrophage-like cell lines and two rat hepatoma cell lines in tissue cultures. A short account covers the extensive literature on regulation of C3 serum concentrations in acute and chronic inflammation and the very incomplete picture that presently depicts hormonal regulation of C3 synthesis. The final experiment reported demonstrates that nucleic acid hybridization with cloned cDNA probes is a sensitive assay for quantitative determinations of C3 mRNA. With the help of cloned cDNA and genomic DNA, researchers can address questions concerning the functional topography of the C3 polypeptide, the gene's structure, and the molecular nature of inherited C3 deficiencies in humans.

Nucleotide sequence of complementary DNA and derived amino acid sequence of murine complement protein C3

“…The com puter programs of Staden (1982 a, b). Approximately 44000 characters of prim ary sequence d ata were generated with the dideoxy-technique in addition to the partial sequence d ata generated with the M axam and Gilbert technique which have previously been published W iebauer et al 1982;Fey et al 1983). Each nucleotide of the cDNA sequence given in figure 1 was sequenced on the average over six times with the dideoxy-technique, and over 95 % of the sequence have been covered by two or more independent gel readings on both of the DNA strands.…”

Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus.

“…3 The a2M gene belongs in a gene family together with the complement C3, C4, and C5 genes. In mice, the C3 and C4 genes reside on the same chromosome, chromosome 17 (54); in humans they reside on different chromosomes: C3 on chromosome 19 (23) and C4 on chromosome 6 (24). Thus, no selective pressure is apparent to maintain these loci on the same chromosome after duplication and divergence.…”

Representational difference analysis of a committed myeloid progenitor cell line reveals evidence for bilineage potential

“…pBluescript and ␤-actin were included on the blot as negative and positive controls, respectively. expressed in EPRO cells, and its expression has been described in mouse macrophage-like cell lines (20). Neutrophil-specific genes include the IL-8 receptor (21), as well as a fragment bearing homology to human neutrophil collagenase.…”