Transmission of autoimmune haemolytic anaemia and murine leukaemia virus to hybrid progeny of allophenic NZB in equilibrium CFW and NZB in equilibrium BALB/c male mice.

The transmission of autoimmune haemolytic anaemia and murine leukaemia virus (MuLV) was studied in 116 progeny of allophenic (tetraparental) NZB↔CFW and NZB↔BALB/c male mice. Of two NZB↔CFW males mated to normal albino BALB/c partners, one proved to have an NZB (black) and the other a CFW (albino) genotype, producing agouti-coloured F1(BALB/c × NZB) and albino F1(BALB/c × CFW) progeny, respectively. But only the agouti offspring developed a protracted course of autoimmune haemolytic disease (positive Coombs tests, anaemia, and splenomegaly), diverse lymphoid, lung, and liver tumours, and carried type C MuLV readily detected by electronmicroscopy. They were identical in all these respects to F1(BALB/c × NZB) hybrids derived naturally. In contrast, no autoimmune haemolytic anaemia, very little virus, and a preponderance of lung tumours, appeared in the albino progeny. A third NZB↔BALB/c male also sired agouti F1 and vari-coloured F2(BALB/c × NZB) hybrids showing the same pattern of autoimmunity, malignancies and virus infection and, when additionally mated to NZB females, produced two generations of black (NZB × NZB) descendants displaying the typical NZB profile of autoimmune haemolytic disease. Thus, only the progeny of allophenic fathers having the NZB genotype expressed autoimmunity and large numbers of MuLV particles. We concluded that infectious virus was not transferred passively by sperm into the ova at fertilization, but that both autoimmunity and virus were transmitted by incorporation of genetic information. The range and type of malignancies were also genetically determined. These results are also consistent with the fact that the sole virus of NZB mice is xenotropic.