Emi Yoshida

The induction of cataracts by HIV-1 in transgenic mice

ObjectiveTo elucidate the tissue specificity of the expression of HIV-1 genes in an animal and its pathological effects on these tissues. Design and methodsTransgenic mice carrying a defective HIV-1 genome were bred in order to overcome the host–range barrier of this virus. ResultsmRNA specific to the transgene was detected in the eyes and the spleen, and, in smaller quantities, in the thymus and the brain. Interestingly, many of the transgenic mice developed cataracts at 3–6 months of age. Swelling and vacuolation of the lens fiber cells were marked, but the epithelial cells of the lens were less affected. HIV antigens were detected in the lens fiber cells and the retina by immunological staining. Accumulation of large amounts of p24 Gag antigen was demonstrated in the affected lens by immunoblot analysis, while negligible Env or other viral proteins was detected. Although accumulation of the Gag protein was also detected in the skin and the brain, no apparent abnormality was observed in these tissues. ConclusionsPreferential expression of the HIV genes in the eyes, skin, brain and lymphoid tissues was demonstrated. The accumulation of the Gag protein is suggested to have detrimental effects on lens fiber cells, causing cataracts.

Induction of interferon-α by interferon-β, but not of interferon-β by interferon-α, in the mouse

Abstract The antigenicity of the interferon (IFN) produced in transgenic mice carrying an extra mouse IFN-β gene under the control of mouse metallothionein-I enhancer-promoter was examined after induction with Cd 2+ . Unexpectedly, IFN-α in addition to IFN-β was detected in the serum. Induction of IFN-α was also observed when recombinant mouse IFN-β was injected into normal mice. IFN-a was first detected in the circulation 6–10 hr after the administration of IFN-β, and after 12 hr, IFN-α became the major component of serum IFN. On the other hand, when IFN-a was injected, no production of IFN-β was observed. Messenger RNAs specific for IFN-α and endogenous IFN-β were detected in the spleen, though the amount of IFN-,B mRNA was much less than that of IFN-a mRNA. These mRNAs were not detected in other organs including the liver where exogenous IFN-β gene was markedly expressed. These observations showed that the expression of IFN-α is inducible by IFN-β in the mouse, and the spleen was suggested to be the main site of production. Possible mechanisms of the induction are discussed.

Augmentation of c-fos and c-jun expression in transgenic mice carrying the human T-cell leukemia virus type-I tax gene

To analyze the effect of human T-cell leukemia virus type I (HTLV-I) on cellular gene expression and its relation to tumorigenesis, two lines of transgenic mice carrying the long terminal repeat (LTR)-env-pX-LTR regions of the HTLV-I genome were produced. The transgene was expressed in many organs, including the brain, salivary gland, spleen, thymus, skin, muscle, and mammary gland. We found that the expression of the c-fos and c-jun genes, but not of thelyn and c-myc genes, was augmented 2- to 20-fold in histologically normal skin and muscle of these mice. The augmentation was tissue specific, suggesting the involvement of a cellular factor in the transgene action. In these mice, a three to seven times higher incidence of tumors was seen as compared with the control mice. These tumors included mesenchymal tumors, such as fibrosarcoma, neurofibroma, and lipoma, and adenocarcinomas of the mammary gland, salivary gland, and lung. The c-fos and c-jun genes were also activated in these tumors. The possible roles of elevated c-fos and c-jun gene expression in tumorigensis are discussed.