Transgenic mice which carry hybrid p53 promoter-chloramphenicol acetyltransferase (CAT) transgenes were found to express CAT enzymatic activity predominantly in the testes. Endogenous levels of p53 mRNA and protein were lower than in the nontransgenic control mice. The various p53 promoter-CAT transgenic mice exhibited in their testes multinucleated giant cells, a degenerative syndrome resulting presumably from the inability of the tetraploid primary spermatocytes to complete meiotic division. The giant-cell degenerative syndrome was also observed in some genetic strains of homozygous p53 null mice. In view of the hypothesis that p53 plays a role in DNA repair mechanisms, it is tempting to speculate that the physiological function of p53 that is specifically expressed in the melotic pachytene phase of spermatogenesis is to allow adequate time for the DNA reshuffling and repair events which occur at this phase to be properly completed. Primary spermatocytes which have reduced p53 levels are probably impaired with respect to DNA repair, thus leading to the development of genetically defective giant cells that do not mature.

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) were employed t o further explore the mode by which this viral protein interacts with cellular metabolism t o change carbohydrate allocation. Dye-coupling experiments established that expression of the TMV-MP alters plasmodesmal function in both potato leaves and tubers when expressed in the respective tissues. However, whereas the sizeexclusion limit of mesophyll plasmodesmata was increased to a value greater than 9.4 kD, this size limit was smaller for plasmodesmata interconnecting tuber parenchyma cells. Starch and sugars accumulated in potato leaves t o significantly lower levels in plants expressing the TMV-MP under the ST-LS1 promoter, and rate of sucrose efflux from petioles of the latter was higher compared to controls. It is interesting that this effect was expressed only in mature plants after tuber initiation. No effect on carbohydrate levels was found in plants expressing this protein under the 833 promoter. These results are discussed in terms of the mode by which the TMV-MP exerts its influence over carbon metabolism and photoassimilate translocation, and the possible role of plasmodesmal function i n controlling these processes.It is generally accepted that most if not a11 viruses move from cell to cell via plasmodesmata. This process requires an interaction between a specific virally encoded protein, termed the MP, and proteins within the plasmodesmata of the host plant . Expression of the TMV-MP in transgenic tobacco plants provided the first evidence that this protein potentiates the short-distance transport of viral infectious material (Deom et al., 1987 Immunolocalization studies indicated that the TMV-MP was localized mainly in secondary plasmodesmata connecting mesophyll cells and bundle-sheath cells to phloem parenchyma cells (Ding et al., 1992). Dye-coupling studies established that the SEL of plasmodesmata interconnecting the mesophyll cells of these transgenic plants was greater than 9.4 kD, as compared to 800 D in control plants, indicating that the TMV-MP has a direct effect on plasmodesmal function (Wolf et al., 1989). Based on plasmodesmal frequencies and dye-coupling experiments, it has been assumed that plasmodesmata play an important role in regulating symplasmic transport (Robards and Lucas, 1990). Pursuant to this assumption, transgenic plants in which plasmodesmata are modified provide an elegant system in which to further test the hypothesis that diffusion of SUC through plasmodesmata acts as a limiting step to symplasmic transport. Our comparative analysis of leaf photosynthetic performance, carbohydrate level, and carbon export in TMV-MP transgenic and control tobacco plants revealed a complex influence of the MP over these parameters (Lucas et al., 1993b;Olesinski et al., 1995). Fully expanded leaves of transgenic tobacco plants expressing the TMV-MP accumulated much higher levels of SUC, Glc, Fru, and starch during the day than did those of control plants. Direct measurements of 14C-photosynthate translocation from source leaves indicated that export was lower in plan...

The tobacco mosaic virus movement protein (TMV-MP) has pleiotropic effects when expressed in transgenic tobacco (Nicotiana tabacum) plants. In addition to its ability to increase the plasmodesmal size-exclusion limit, the TMV-MP alters carbohydrate metabolism in source leaves and dry matter partitioning between the various plant organs. In the present study the TMV-MP was expressed under the control of a phloem-specific promoter (rolc), and this system was employed to further explore the potential sites at which the TMV-MP exerts its influence over carbon metabolism and transport in transgenic potato (Solanum tuberosum) plants. Immunohistochemical analyses indicated that the TMV-MP was localized mainly to phloem parenchyma and companion cells. Starch and sucrose accumulated in source leaves of these plants to significantly higher levels compared with control potato lines. In addition, the rate of sucrose efflux from excised petioles was lower compared with control plants. Furthermore, under short-day conditions, carbon partitioning was lower to the roots and higher to tubers in rolC plants compared with controls. These results are discussed in terms of the mode(s) by which the TMV-MP exerts its influence over carbon metabolism and photoassimilate translocation.

Plants are a promising alternative for the production of biotherapeutics. Manufacturing in-planta adds plant specific glycans. To understand immunogenic potential of these glycans, we developed a validated method to detect plant specific glycan antibodies in human serum. Using this assay, low prevalence of pre-existing anti-plant glycan antibodies was found in healthy humans (13.5%) and in glucocerebrosidase-deficient Gaucher disease (GD) patients (5%). A low incidence (9% in naïve patient and none in treatment experienced patients) of induced anti-plant glycan antibodies was observed in GD patients after up to 30 months replacement therapy treatment with taliglucerase alfa, a version of human glucocerebrosidase produced in plant cells. Detailed evaluation of clinical safety and efficacy endpoints indicated that anti-plant glycan antibodies did not affect the safety or efficacy of taliglucerase alfa in patients. This study shows the benefit of using large scale human trials to evaluate the immunogenicity risk of plant derived glycans, and indicates no apparent risk related to anti-plant glycan antibodies.

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