Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development

We have constructed a transgenic mouse strain in which a mammary tumor virus LTR/c-myc fusion gene is anomalously expressed in a wide variety of tissues. The deregulated c-myc transgene, now glucocorticoid inducible, contributes to an increased incidence of a variety of tumors, including those of testicular, breast, lymphocytic (B cell and T cell), and mast cell origin. The deregulated gene does not, however, otherwise disturb cell proliferation, nor does it interfere with normal development in these animals. Moreover, since not all tissues that express the transgene develop neoplasms, these results begin to define the transforming spectrum of the c-myc oncogene. They also extend to several organ systems the notion that elements in addition to an activated c-myc gene are required to induce malignancy in the living organism.     

Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene

We have used transgenic mice that carry an activated c-neu oncogene driven by a mouse mammary tumor virus (MMTV) promoter to assess the stepwise progression of carcinogenesis in mammary epithelium. Unlike the stochastic occurrence of solitary mammary tumors in transgenic mice bearing the MMTV/c-myc or the MMTV/v-Ha-ras oncogenes, transgenic mice uniformly expressing the MMTV/c-neu gene develop mammary adenocarcinomas that involve the entire epithelium in each gland. Because these tumors arise synchronously and are polyclonal in origin, expression of the activated c-neu oncogene appears to be sufficient to induce malignant transformation in this tissue in a single step. In contrast, expression of the c-neu transgene in the parotid gland or epididymis leads to benign, bilateral epithelial hypertrophy and hyperplasia which does not progress to full malignant transformation during the observation period. These results indicate that the combination of activated oncogene and tissue context are major determinants of malignant progression and that expression of the activated form of c-neu in the mammary epithelium has particularly deleterious consequences.     

Deletion of a GC-rich region flanking the enhancer element within the long terminal repeat sequences alters the disease specificity of Moloney murine leukemia virus.

Moloney murine leukemia virus (M-MuLV) is a replication-competent retrovirus which induces T-lymphoblastic lymphoma 2 to 4 months after inoculation. Enhancer sequences in the U3 region of the M-MuLV long terminal repeat, primarily the 75-bp tandem repeats, strongly influence the disease specificity and latency of M-MuLV. We investigated the role of GC-rich sequences downstream of the tandem repeats in the disease specificity of M-MuLV. A recombinant M-MuLV lacking 23 bases of a GC-rich sequence (-174 to -151), Delta 27A M-MuLV, was tested for pathogenesis in neonatal NIH Swiss mice. Delta 27A M-MuLV induced disease with a longer latency than did M-MuLV (7 versus 3 months) in greater than 85% of inoculated mice. More interestingly, this virus showed an expanded repertoire of hematopoietic diseases. Molecular analyses and histopathologic examinations indicated that while 39% of mice inoculated with Delta 27A M-MuLV developed T-cell lymphoblastic lymphoma typical of wild-type M-MuLV, the majority developed acute myeloid leukemia, erythroleukemia, or B-cell lymphoma. Viral DNA corresponding to Delta 27A M-MuLV was detectable in most of the tumors analyzed. These findings indicate that the GC-rich region significantly influences the disease specificity and latency of M-MuLV.     

The int-2 gene product acts as an epithelial growth factor in transgenic mice.

The induction of mammary tumors by mouse mammary tumor virus (MMTV) is thought to occur through proviral activation of one or more cellular genes. One of these, int-2, encodes a 27 kd protein which exhibits striking homology to the basic fibroblast growth factor family. To assess directly the role of the int-2 protein in cell proliferation, we have established transgenic mice which carry the int-2 gene driven by the MMTV promoter/enhancer. Expression of the int-2 gene in female transgenic mice results in pronounced mammary gland hyperplasia. Interestingly, expression of the MMTV-int-2 transgene in the prostate gland of male carriers results in a benign, but dramatic, epithelial hyperplasia similar to benign prostatic hypertrophy (BPH), a common but poorly understood disorder in human populations. Together, these results indicate that the int-2 product can act as a potent growth factor in these epithelial tissues.     

Biological characterization of uncleavable plasma membrane-anchored human macrophage colony-stimulating factor

The cell-surface form of human macrophage colony-stimulating factor (CSF-1(256), M-CSFalpha) is a plasma membrane-anchored transmembrane protein from which the soluble CSF-1 is released by ectodomain proteolytic cleavage. We have previously generated two forms of cell surface CSF-1 which failed to undergo the cleavage by deleting residues 161-165 or residues 159-165 in the extracellular juxtamembrane region (1). To determine the biologic significance of the ectodomain cleavage, we compared the biosynthesis and biologic activities of uncleavable mutant CSF-1 forms with those of the cleavable wild-type (WT) CSF-1. We found that the uncleavable CSF-1 forms were able to accumulate on cell surface at about threefold higher level than the cleavable WT CSF-1 did. We further demonstrated that the uncleavable plasma membrane-anchored forms of CSF-1 were biologically active in mediating the proliferation of CSF-1-dependent cells as well as the intercellular adhesion between CSF-1 receptor-bearing cells and CSF-1 expressing cells. Furthermore, the adhesive activity of uncleavable CSF-1 forms was about twofold stronger than that of WT CSF-1, which indicated that the ectodomain cleavage system plays an important role in regulating the biologic activities of membrane-anchored CSF-1.     

棉花和香瓜的甘薯粉虱Bemisia tabaci (同翅目 ,粉虱科 )B生态型虫体大小和重量的田间调查(英文)

20 0 0和 2 0 0 1年在美国凤凰城和北达科塔州法哥城田间 ,调查棉花和香瓜上甘薯粉虱BemisiatabaciB生态型所有虫期虫体大小和重量。从若虫大小计算出若虫的体积。第一到第四龄晚期 ,若虫平均体积以指数方式增加。体积增加最快的是第三到第四龄早期。棉花上的若虫比香瓜上的宽 ,但是并不比较长。香瓜上第一到第四龄早期的若虫 ,最厚部位的腹部和背部厚度比例显著比棉花上的要高。两种寄主作物上的若虫从第一到第四龄发育期 ,腹部厚度平均增加将近 5 1倍 ,而背部厚度只增加 2 8倍。雌虫和雄虫从头顶到翅尖平均长度分别为 112 6和 95 3微米 ,重量为 39和 17微克。棉花和香瓜上的虫卵平均长 ,宽 ,重分别为 197微米 ,99微米 ,和0 8微克。未被寄生的蛹壳长 ,宽 ,重分别为 6 73微米 ,4 92微米和 1 2微克 ;被寄生的蛹壳为 6 6 5微米 ,4 5 2微米 ,和 3 6微克。棉花上未被寄生和被寄生的蛹壳比香瓜上的长 ,宽 ,和更重。     

Gas exchange patterns of Pterostichus niger (Carabidae) in dry and moist air

Gas exchange patterns of adult male Pterostichus niger Schaller after hydration (i.e. given access to food and water) are compared in dry air [5–7% relative humidity (RH)] and moist air (90–97% RH) by means of flow‐through CO₂ respirometry combined with infrared probe actography. Of thirty beetles examined, slightly more than 50% showed continuous gas exchange and are not considered further. Of the remaining beetles, the majority (approximately 71%) display a pattern of cyclic gas exchange in both dry and moist air (i.e. CO₂ gas is released in bursts, with a low level of CO₂ release during the interburst periods). A minority of the beetles (four out of 30) are found to exhibit discontinuous gas exchange in both dry and moist air; this is characterized by three clearly separated states of the spiracles: closed (C), flutter (F) and open (O) phases. The pattern of cyclic gas exchange is associated with weak abdominal pulsations. After switching from moist to dry air, a small modulation of the discontinuous gas exchange cycles (maximum mean CO₂ production rate) occurs, providing no clear support for the hygric theory of discontinuous gas exchange in this species (i.e. that it serves to restrict respiratory water loss).     

Record of Blue tilapia Oreochromis aureus (Steindachner, 1864) in the Eerste River catchment,Western Cape province,South Africa

Oreochromis aureus was imported from Israel into South Africa in 1959 but data on its current status in South Africa are lacking. Genomic DNA was extracted and the COI gene amplified at the South African Institute for Aquatic Biodiversity. The identity of the sequences and specimens was determined using the Barcode of Life Data Systems and GenBank. Morphological and genetic assessment demonstrated that 11 specimens collected from two farm dams in the Eerste River System, Western Cape province, were Oreochromis aureus. A MaxEnt model compiled using global distribution, rainfall and temperature data predicted that large areas of southern Africa were climatically suitable for this species, indicating considerable invasion debt in southern Africa. As a result, surveys to assess for the extent of the invasion in South Africa and eradication of existing populations, if feasible, are recommended management actions.