MOLECULAR ANALYSIS OF THE THIRD COMPONENT OF CANINE COMPLEMENT-(C3) AND IDENTIFICATION OF THE MUTATION RESPONSIBLE FOR HEREDITARY CANINE C3DEFICIENCY

Genetically determined deficiency of the third component of complement (C3) in the dog is characterized by a predisposition to recurrent bac terial infections and to type 1 membranoproliferative glomerulonephrit is. The current studies were undertaken to characterize the cDNA for w ild-type canine C3 and identify the molecular basis for hereditary can ine C3 deficiency, Amplification, cloning, and sequence analysis indic ated that canine C3 is highly conserved in comparison with human, mous e, and guinea pig C3. Southern blot analysis failed to show any gross deletions or rearrangements of DNA from C3-deficient animals, Northern blot analysis indicated that the livers of these animals contain mark edly reduced quantities of a normal length C3 mRNA, The full-length 5. 1-kb canine C3 cDNA mas amplified in overlapping PCR fragments, Sequen ce analysis of these fragments has shown a deletion of a cytosine at p osition 2136 (codon 712), leading to a frameshift that generates a sto p codon 11 amino acids downstream, The deletion has been confirmed in genomic DNA, and its inheritance has been demonstrated by allele-speci fic oligonucleotide hybridization.