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Starting from distinct foundation populations of outbred mice 5 selections were carried out by bidirectional assortative breeding for high (H) or low (L) antibody responsiveness to natural immunogens. In each selection the assortative mating of the highest responder mice generated the H line while that of the lowest responder mice the L line. High or low antibody responsiveness resulted from the interaction of alleles, at several independent loci, which accumulated progressively in H and L mice during the consecutive generations of selective breeding. Several immune parameters and associated traits were differently affected in the 5 selections, indicating that non equivalent sets of genes were involved. Homologous H or L mice of the 5 selections were intercrossed to produce the F0H or F0L foundation population with a balanced frequency of the gene pools of the lines. After 16 generations the interline difference in antibody titer to the selection antigens, as well as to other unrelated antigens, was much larger in the GS selection as compared to the previous 5 selections suggesting that more genes with upward effects had accumulated in H mice or more genes with downward effects had accumulated in L mice during the GS selection. Accumulation of genes with negative effects on immune responsiveness entails a profound life span shortening and a great increase in lymphoma incidence. The finding of a clear maternal effect for life span and lymphoma incidence suggests the possible involvement of environmental factors that influence these phenotypes during the selection of genes that affect antibody responsiveness.

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Authors: CORELLI V ET AL, ENEA Casaccia, Roma (IT)
Bibliographic Reference: Article : Aging (1995)
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