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Hereditary C3 hypocomplementemia in the rabbit
M Komatsu1, K Yamamoto, Y Nakano
1Department of Animal Breeding and Genetics, National Institute of Animal Industry, Tsukuba, Ibaraki, Japan.
Insights
Hereditary hypocomplementemia of the third component of complement (C3) in rabbits is a co-dominant trait. These rabbits exhibit reduced C3 levels, impacting survival and bactericidal activity.
Area of Science:
- Immunology
- Genetics
Background:
- Hereditary hypocomplementemia of the third component of complement (C3) was identified in a rabbit strain.
- This strain also exhibited hereditary C8 alpha-gamma deficiency.
Purpose of the Study:
- To characterize the hereditary C3 hypocomplementemia in rabbits.
- To investigate the genetic transmission and functional consequences of this condition.
Main Methods:
- Quantification of serum C3 concentration, C3 hemolytic activity, and total hemolytic activity (CH50).
- Functional assays involving addition of purified C3.
- Analysis of other complement components and factors.
- Genetic mating tests and survival studies.
- Assessment of bactericidal activity.
Main Results:
- C3-hypocomplementemic (C3-hypo) rabbits showed significantly reduced C3 levels (6-12%) and hemolytic activity (8-13%), with CH50 at 27-37% of normal.
- Hemolytic activity was restored by adding purified C3, indicating a deficiency in C3 itself.
- Levels of factors H, properdin, C2, and C6 were normal; factors B, D, and C8 were elevated.
- Low C3 levels were not due to conversion, inhibitors, or hypercatabolism.
- C3 hypocomplementemia is inherited as an autosomal co-dominant trait.
- C3-hypo rabbits had lower survival rates and reduced serum bactericidal activity.
Conclusions:
- Hereditary C3 hypocomplementemia in rabbits is a distinct genetic trait.
- This condition leads to impaired immune function, evidenced by reduced bactericidal activity and lower survival.
- The C8 deficiency in this strain does not influence C3 levels or catabolism.
Abstract:
Hereditary hypocomplementemia of the third component of complement (C3) was found in a strain of rabbits in which hereditary C8 alpha-gamma deficiency was also found. The serum C3 concentration, haemolytic C3 activity and total complement haemolytic activity (CH50) of these animals were, respectively, 6-12%, 8-13% and 27-37% of the normal levels. The haemolytic complement activity in the C3 hypocomplementemic (C3-hypo) rabbit serum was restored in a dose-dependent manner by the addition of purified rabbit C3. The levels of factor H and properdin and components C2 and C6 were in the normal range, and the levels of factors B and D and component C8 were higher than normal. The low level of serum C3 in C3-hypo rabbits was not due to C3 conversion, partial C3 antigenicity, presence of a C3 inhibitor or hypercatabolism of normal C3. Furthermore, no change in the ratio of C3 protein levels was observed between C3-hypo and normal rabbits, even after turpentine injection. In addition, the C8 alpha-gamma deficiency condition does not affect C3 activity and C3 catabolism in vivo. Mating tests showed that the C3 hypocomplementemia is transmitted as a simple autosomal co-dominant trait. C3-hypo rabbits have a lower survival at 3 months than normal rabbits. C3-hypo rabbit serum also has a lower bactericidal activity than normal rabbit serum. The PAGE under reducing conditions showed no difference in the molecular weights of C3 alpha and C3 beta chains between C3-hypo, heterozygous and normal animals.