Assuntos
Anemia Hemolítica Autoimune/etiologia , Vírus da Leucemia Murina/patogenicidade , Camundongos Endogâmicos NZB , Anemia Hemolítica Autoimune/genética , Anemia Hemolítica Autoimune/transmissão , Animais , Vírus da Leucemia Murina/isolamento & purificação , Leucemia Experimental/genética , Leucemia Experimental/imunologia , Leucemia Experimental/transmissão , Camundongos , Replicação ViralRESUMO
F1(BALB/c X NZB)hybrid progeny derived by ovum transplantation were used to study the transmission of auto-immune haemolytic anaemia and murine leukaemia virus (MuLV) by male New Zealand black (NZB) mice. Fertilized ova, collected from the normal BALB/c partners 3 1/2 days after mating, were transferred to other, surrogate, BALB/c mothers, which then carried, delivered, and reared the hybrid young. This technical manoeuvre effectively closed the congenital transplacental route theoretically available to any infectious MuLV originating from the NZB father. Nevertheless, such progeny developed exactly the same profile of auto-immune haemolytic disease and the same range of diverse malignancies as their normally-derived F1(BALB/c X NZB) counterparts, and they carried type C MuLV particles readily detectable by electronmicroscopy. We concluded, therefore, that both the auto-immunity and virus were transmitted before placentation, presumably by the NZB male at fertilization, and probably as genetic information.
Assuntos
Anemia Hemolítica Autoimune/transmissão , Vírus da Leucemia Murina/isolamento & purificação , Animais , Teste de Coombs , Feminino , Fertilização , Nefropatias/imunologia , Leucemia/microbiologia , Neoplasias Hepáticas/etiologia , Neoplasias Pulmonares/etiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NZB , Óvulo/transplante , Esplenomegalia/etiologia , Transplante HomólogoRESUMO
When mated to normal BALB/c partners, male and female NZB mice transmitted auto-immune haemolytic anaemia to three generations of their hybrid progeny. Red cell auto-antibodies (positive Coombs tests) were detected, on average, 11 months later in the F1 hybrids than in the parental strain, and the course of the disease was protracted. In explicably, the auto-immune reactions then appeared progressively earlier in successive generations of both croses. The Coombs reactions of the F1 and F2 hybrids were often weak and inconsistent, while those of F3 offspring showed the strong and stable picture typical of NZB mice. The incidence of auto-immune disease in each generation, although similar in the reciprocal crosses, indicated that the pattern of inheritance was very complex. The hybrids did not develop the lymphoid type B reticulum cell neoplasia which characterizes auto-immune NZB mice. Instead, and irrespective of Coombs status, they had lymphocytic leukaemias, lung adenomas, hepatomas and type A reticulum cell neoplasms of the liver. Murine leukaemia virus was identified electronmicroscopically in F1 embryos, and in all the adults examined. It was also isolated from leukaemic spleen cells passaged briefly in vivo, and from malignant hepatic (reticulum) cells maintained in vitro. These isolated were leukaemogenic in newborn BALB/c, NZB, and F1 hybrid recipients, but did not induce or accelerate positive Coombs reactions. Only a small proportion of the hybrids had significant glomerulonephritis, and overt kidney disease was minimal. The lesions were not confined to Coombs-positive mice. Possible links between auto-immunity, malignancy, and virus infection in NZB mice are discussed in the light of these results.