Genetic basis of Complement 3 deficiency in dogs - is an autosomal recessive inherited disorder caused by a frameshift mutation—a deletion of a cytosine at position 2136 in the C3 gene. This mutation leads to a premature stop codon, causing truncated, non-functional C3 protein. C3 is a crucial protein in the complement system, essential for opsonization, immune clearance, and inflammation processes.The deficiency leads to severely reduced C3 levels in plasma, impairing immune response.
Pathophysiology - Deficiency impairs the classical, alternative, and lectin pathways of the complement system. Dogs cannot effectively clear bacterial pathogens, leading to recurrent bacterial infections. Common infections include skin infections, pneumonia, sepsis, pyometra, and other pyogenic bacterial infections. There is an increased risk of type 1 membranoproliferative glomerulonephritis, a kidney disease associated with immune-complex deposition. Immunologic impairments include reduced antibody responses and deficient phagocytosis.
Complications - Recurrent infections especially with encapsulated bacteria. Infections may be severe, prolonged, and difficult to treat. Possible development of immune complex-mediated kidney disease. Susceptibility to infections from a young age, often with serious complications.
Why This Matters to Breeders and Vets - Breeders: Genetic testing helps identify carriers and avoid breeding two carriers, preventing affected pups. Vets: Awareness aids diagnosis in dogs with recurrent infections and guides supportive care such as infection prevention, vaccination, and antibiotics. The disease is lifelong, and management focuses on preventing and treating infections promptly.