Genetic Engineering of Polyamine Catabolism in Transgenic Mice and Rats

2006 ◽  
pp. 465-477
Author(s):  
Juhani Jänne ◽  
Leena Alhonen ◽  
Marko Pietilä ◽  
Tuomo A. Keinänen ◽  
Suvikki Suppola ◽  
...  
Keyword(s):  
Genetic Engineering ◽  
Transgenic Mice ◽  
Polyamine Catabolism

„Gentlemen in, Genuine Knowledge out“? Zum Status wissenschaftlicher Normen für die Erkenntnissicherung

2016 ◽  
Vol 38 (2) ◽  
Author(s):  
Lara Huber
Keyword(s):  
Genetic Engineering ◽  
Transgenic Mice ◽  
Case Studies ◽  
History Of Science ◽  
Science And Technology ◽  
Scientific Practices ◽  
History Of ◽  
Genuine Knowledge

ZusammenfassungCase studies in the history of science and technology have shown that scientific norms, so called standards, contribute significantly to the evolution of scientific practices. They arise predominantly, but not exclusively, on the basis of interactions with instruments of measurement and other technical devices. As regards experimental practices standards are mandatory preparatory procedures in a variety of designs, including the inbreeding and genetic engineering of experimental organisms (e.g. transgenic mice). I claim that scientific norms not only regulate mere technical preconditions of research but also guide experimental practices, for example with regard to the stabilisation and validation of phenomena. Against this background, the paper introduces different kinds of scientific norms and elaborates on the question if they are means to epistemic ends (e.g. stability).

Concurrent overexpression of ornithine decarboxylase and spermidine/spermine N1-acetyltransferase further accelerates the catabolism of hepatic polyamines in transgenic mice

2001 ◽  
Vol 358 (2) ◽  
pp. 343-348 ◽  
Author(s):  
Suvikki SUPPOLA ◽  
Sami HEIKKINEN ◽  
Jyrki J. PARKKINEN ◽  
Mikko UUSI-OUKARI ◽  
Veli-Pekka KORHONEN ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Ornithine Decarboxylase ◽  
Transgenic Animals ◽  
Transgenic Mouse Line ◽  
Polyamine Catabolism ◽  
Permanent Loss ◽  
Organ Specific ◽  
Polyamine Analogue ◽  
Efflux Mechanism ◽  
Ssat Activity

We have generated a hybrid transgenic mouse line overexpressing both ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SSAT) under the control of the mouse metallothionein (MT) I promoter. In comparison with singly transgenic animals overexpressing SSAT, the doubly transgenic mice unexpectedly displayed much more striking signs of activated polyamine catabolism, as exemplified by a massive putrescine accumulation and an extreme reduction of hepatic spermidine and spermine pools. Interestingly, the profound depletion of the higher polyamines in the hybrid animals occurred in the presence of strikingly high ODC activity and tremendous putrescine accumulation. Polyamine catabolism in the doubly transgenic mice could be enhanced further by administration of zinc or the polyamine analogue N1,N11-diethylnorspermine. In tracer experiments with [14C]spermidine we found that, in comparison with syngenic animals, both MT-ODC and MT-SSAT mice possessed an enhanced efflux mechanism for hepatic spermidine. In the MT-ODC animals this mechanism apparently operated in the absence of measurable SSAT activity. In the hybrid animals, spermidine efflux was stimulated further in comparison with the singly transgenic animals. In spite of a dramatic accumulation of putrescine and a profound reduction of the spermidine and spermine pools, only marginal changes were seen in the level of ODC antizyme. Even though the hybrid animals showed no liver or other organ-specific overt toxicity, except an early and permanent loss of hair, their life span was greatly reduced. These results can be understood from the perspective that catabolism is the overriding regulatory mechanism in the metabolism of the polyamines and that, even under conditions of severe depletion of spermidine and spermine, extremely high tissue pools of putrescine are not driven further to replenish the pools of the higher polyamines.

scholarly journals Activation of Polyamine Catabolism Profoundly Alters Tissue Polyamine Pools and Affects Hair Growth and Female Fertility in Transgenic Mice Overexpressing Spermidine/SpermineN1-Acetyltransferase

1997 ◽  
Vol 272 (30) ◽  
pp. 18746-18751 ◽  
Author(s):  
Marko Pietilä ◽  
Leena Alhonen ◽  
Maria Halmekytö ◽  
Peter Kanter ◽  
Juhani Jänne ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Hair Growth ◽  
Female Fertility ◽  
Polyamine Catabolism

Quantitative Microscopic Comparison of the Organization of the Lung in Transgenic Mice Expressing Transforming Growth Factor-α (TGF-α)

1996 ◽  
Vol 54 ◽  
pp. 14-15
Author(s):  
C. G. Plopper ◽  
C. Helton ◽  
A. J. Weir ◽  
J. A. Whitsett ◽  
T. R. Korfhagen
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Transgenic Mice ◽  
Blood Vessels ◽  
Lung Parenchyma ◽  
Lung Maturation ◽  
Alveolar Air ◽  
Parenchymal Tissue ◽  
Air Space ◽  
Conducting Airways

A wide variety of growth factors are thought to be involved in the regulation of pre- and postnatal lung maturation, including factors which bind to the epidermal growth factor receptor. Marked pulmonary fibrosis and enlarged alveolar air spaces have been observed in lungs of transgenic mice expressing human TGF-α under control of the 3.7 KB human SP-C promoter. To test whether TGF-α alters lung morphogenesis and cellular differentiation, we examined morphometrically the lungs of adult (6-10 months) mice derived from line 28, which expresses the highest level of human TGF-α transcripts among transgenic lines. Total volume of lungs (LV) fixed by airway infusion at standard pressure was similar in transgenics and aged-matched non-transgenic mice (Fig. 1). Intrapulmonary bronchi and bronchioles made up a smaller percentage of LV in transgenics than in non-transgenics (Fig. 2). Pulmonary arteries and pulmonary veins were a smaller percentage of LV in transgenic mice than in non-transgenics (Fig. 3). Lung parenchyma (lung tissue free of large vessels and conducting airways) occupied a larger percentage of LV in transgenics than in non-transgenics (Fig. 4). The number of generations of branching in conducting airways was significantly reduced in transgenics as compared to non-transgenic mice. Alveolar air space size, as measured by mean linear intercept, was almost twice as large in transgenic mice as in non-transgenics, especially when different zones within the lung were compared (Fig. 5). Alveolar air space occupied a larger percentage of the lung parenchyma in transgenic mice than in non-transgenic mice (Fig. 6). Collagen abundance was estimated in histological sections as picro-Sirius red positive material by previously-published methods. In intrapulmonary conducting airways, collagen was 4.8% of the wall in transgenics and 4.5% of the wall in non-transgenic mice. Since airways represented a smaller percentage of the lung in transgenics, the volume of interstitial collagen associated with airway wall was significantly less. In intrapulmonary blood vessels, collagen was 8.9% of the wall in transgenics and 0.7% of the wall in non-transgenics. Since blood vessels were a smaller percentage of the lungs in transgenics, the volume of collagen associated with the walls of blood vessels was five times greater. In the lung parenchyma, collagen was 51.5% of the tissue volume in transgenics and 21.2% in non-transgenics. Since parenchyma was a larger percentage of lung volume in transgenics, but the parenchymal tissue was a smaller percent of the volume, the volume of collagen associated with parenchymal tissue was only slightly greater. We conclude that overexpression of TGF-α during lung maturation alters many aspects of lung development, including branching morphogenesis of the airways and vessels and alveolarization in the parenchyma. Further, the increases in visible collagen previously associated with pulmonary fibrosis due to the overexpression of TGF-α are a result of actual increases in amounts of collagen and in a redistribution of collagen within compartments which results from morphogenetic changes. These morphogenetic changes vary by lung compartment. Supported by HL20748, ES06700 and the Cystic Fibrosis Foundation.

Eleveted serum gastrin level cannot maintain basal and stimulated gastric acid secretion in histamine deficient transgenic mice

2001 ◽  
Vol 120 (5) ◽  
pp. A180-A180
Author(s):  
B HUNYADY ◽  
A ZOLYOMI ◽  
J CZIMMER ◽  
G MOZSIK ◽  
E BUZAS ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Serum Gastrin ◽  
Gastrin Level ◽  
Serum Gastrin Level

Transgenic Mice

1992 ◽  
Vol 25 (5) ◽  
pp. 1017-1026 ◽  
Author(s):  
Rick A. Friedman ◽  
Allen F. Ryan
Keyword(s):  
Transgenic Mice
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