Milk-borne Mammary Tumor Virus Research Articles

Expression of mouse mammary tumor virus superantigen mRNA in the thymus correlates with kinetics of self-reactive T-cell loss.

Mouse mammary tumor virus (MMTV) encodes a superantigen (Sag) that is expressed at the surface of antigen-presenting cells in conjunction with major histocompatibility complex (MHC) type II molecules. The Sag-MHC complex is recognized by entire subsets of T cells, leading to cytokine release and amplification of infected B and T cells that carry milk-borne MMTV to the mammary gland. Expression of Sag proteins from endogenous MMTV proviruses carried in the mouse germ line usually results in the deletion of self-reactive T cells during negative selection in the thymus and the elimination of T cells required for infection by specific milk-borne MMTVs. However, other endogenous MMTVs are unable to eliminate Sag-reactive T cells in newborn mice and cause partial loss of reactive T cells in adults. To investigate the kinetics of Sag-reactive T-cell deletion, backcross mice that contain single or multiple MMTVs were screened by a novel PCR assay designed to distinguish among highly related MMTV strains. Mice that contained Mtv-17 alone showed slow kinetics of reactive T-cell loss that involved the CD4(+), but not the CD8(+), subset. Deletion of CD4(+) or CD8(+) T cells reactive with Mtv-17 Sag was not detected in thymocytes. Slow kinetics of peripheral T-cell deletion by Mtv-17 Sag also was accompanied by failure to detect Mtv-17 sag-specific mRNA in the thymus, despite detectable expression in other tissues, such as spleen. Together, these data suggest that Mtv-17 Sag causes peripheral, rather than intrathymic, deletion of T cells. Interestingly, the Mtv-8 provirus caused partial deletion of CD4(+)Vbeta12(+) cells in the thymus, but other T-cell subsets appeared to be deleted only in the periphery. Our data have important implications for the level of antigen expression required for elimination of self-reactive T cells. Moreover, these experiments suggest that mice expressing endogenous MMTVs that lead to slow kinetics of T-cell deletion will be susceptible to infection by milk-borne MMTVs with the same Sag specificity.

The Icr:Ha(ICR) mouse: a current account of breeding, mutations, diseases and mortality.

This stock of albino mice is minimally inbred (0.5% per generation), and has been rigidly selected for fecundity. It is widely employed in oncological and pharmaceutical research. Spontaneous tumours arose in 55% of animals, multiple in 28%, averaging 1.66 per mouse. Females developed tumours at an earlier age than males. Predominant tumour types were pulmonary (23.1%), lymphoreticular (20%), and mammary (14%--23% of females). Miscellaneous tumour types (42.9%) ranged in frequency from 0.2 to 2.0%, the latter being hepatomas. Distribution of mammary tumours indicated that milk-borne mammary tumour virus was absent. Non-neoplastic disease was present in 58.6%, 24.1% being pulmonary and predominant in the young, while renal (31.2%) and cardiovascular (10.2%) disease was common in the elderly. Males outlived females.

Response of C3H-A vy fB Female Mice to a Low Oncogenic, Milk-Borne Mammary Tumor Virus

When low oncogenic milk-borne mammary tumor virus (MTV) of strain DD was tested in C3H-AvyfB mice, as compared with the similar strain C3HfB, mammary tumors occurred with a higher incidence and at lower age in C3H-AvyfBfDD (with DD-MTV) than in C3HfBfDD (with DD-MTV), as observed in virgin females. Since the effect of breeding tended to mask any difference between the breeders, mammary tumor incidences were similar with a slightly higher age at tumor occurrence in the C3H-AvyfBfDD females. Thus the C3H-AvyfB virgins (with the Avy gene) were almost as susceptible to mammary tumors with the less potent DD-MTV as were C3HfB virgins with the more virulent C3H-MTV of strain C3H.

Possibility of a DNA-containing Mammary Tumour Virus in Red Blood Cells of Mouse

THE classical mammary tumour virus (MTV), also referred to as the Bittner virus, is transmitted in milk from mother to offspring. Studies1–4 of the fate and biological behaviour of MTV in BALB/cfC3H (C+) mice suggested to us that MTV goes through a cycle in the infected host. Milk-borne MTV (M-MTV), assumed to be B particles, is abundantly present in milk and mammary tissues of infected mice. It seems likely that, on entering the host, M-MTV first infects the erythropoietic cells; subsequently the virus is carried into the general circulation chiefly inside the reticulocyte fraction2 of red blood cells (RBC) in a form which we have called R-MTV4. We have also suggested4 that, in the MTV cycle, R-MTV functions in the infection of mammary tissues, which are the primary sites of production of M-MTV (or B particles). The latter form of the virus, in turn, is involved in the transport of the viral genome to the young through milk.