scholarly journals Re-transmissibility of mouse-adapted ME7 scrapie strain to ovine PrP transgenic mice

2019 ◽  
Vol 20 (2) ◽  
Author(s):  
Joshua Adekunle Babalola ◽  
Jong-Mu Kim ◽  
Yun-Jung Lee ◽  
Jeong-Ho Park ◽  
Hong-Seok Choi ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Scrapie Strain

Hamster Prions Are a Suitable Model for Partitioning of Human CJD Prions during Plasma Processing Steps.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3644-3644
Author(s):  
Albrecht Groener ◽  
Wolfram Schäfer ◽  
Henry Baron ◽  
Martin Vey
Keyword(s):  
Transgenic Mice ◽  
Human Plasma ◽  
Evaluation Studies ◽  
Plasma Processing ◽  
Reduction Factor ◽  
Membrane Preparation ◽  
Suitable Model ◽  
Ethanol Precipitation ◽  
Removal Capacity ◽  
Scrapie Strain

Abstract Prion removal evaluation of plasma processing procedures is one important basis to assess the margin of safety of plasma protein therapeutics. Currently, in these evaluation studies to assess the removal capacity of selected manufacturing steps for human prions mainly prions derived from scrapie-infected hamsters or mice are used in spiking studies. In order to test the validity of hamster prions instead of different human prion strains as spiking reagents, we compared the partitioning of these prion preparations at two purification steps common to the manufacturing of several human plasma-derived therapeutic proteins at ZLB Behring. The glycine precipitation (inherent in the manufacture of e.g., vWF/Factor VIII) and the 25% ethanol precipitation step (inherent in the manufacture of e.g., alpha-1-proteinase inhibitor and albumin) were down scaled to mimic the production process. A microsomal membrane preparation as well as purified full-length pathogenic prion (PrPSc; without membrane association) prepared (a) from hamster brains infected with the model scrapie strain Sc237, (b) from brains of transgenic mice infected with human sporadic CJD prions, and (c) from the brain of a patient who died of vCJD were used for spiking experiments. The different prion preparations were spiked to the starting material of the manufacturing steps studied and the manufacturing step was performed in a dedicated laboratory. The amount of PrPSc in all fractions was determined quantitatively utilizing an ELISA-formatted Conformation Dependent Immunoassay [Safar et al., Nat Med1998; 41157–1165]. The 25% ethanol precipitation removed very effectively all prion preparations equally regardless of their origin (reduction factor ≥ 3 log10). The glycine precipitation removed the microsomal as well as the purified prion preparations from all species equally whereby prions of the purified prion preparation were removed to a considerably higher degree than the membrane preparation (reduction factor ≥ 3 log10 vs. 1.6 to 1.8 log10). In parallel, prion infectivity of each sample is currently tested in animal bioassays involving transgenic mice susceptible for the tested prion strain. It can be concluded, up to now based on immunological data, that spiked hamster prions are a reliable model to confirm the safety of human plasma-derived products also for human derived prions.

Scrapie strain transmission studies in ovine PrP transgenic mice reveal dissimilar susceptibility

2007 ◽  
Vol 127 (5) ◽  
pp. 531-539 ◽  
Author(s):  
Anna Bencsik ◽  
Sandrine Philippe ◽  
Sabine Debeer ◽  
Carole Crozet ◽  
Didier Calavas ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Scrapie Strain ◽  
Transmission Studies

scholarly journals Breaking an Absolute Species Barrier: Transgenic Mice Expressing the Mink PrP Gene Are Susceptible to Transmissible Mink Encephalopathy

2005 ◽  
Vol 79 (23) ◽  
pp. 14971-14975 ◽  
Author(s):  
O. Windl ◽  
M. Buchholz ◽  
A. Neubauer ◽  
W. Schulz-Schaeffer ◽  
M. Groschup ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Incubation Time ◽  
American Mink ◽  
Infectious Agent ◽  
Laboratory Mice ◽  
Species Barrier ◽  
The North ◽  
Scrapie Strain ◽  
Transmissible Mink Encephalopathy ◽  
Prp Gene

ABSTRACT Transmissible mink encephalopathy (TME) is a rare disease of the North American mink, which has never been successfully transmitted to laboratory mice. We generated transgenic mice expressing the mink prion protein (PrP) and inoculated them with TME or the mouse-adapted scrapie strain 79A. TME infected mink PrP-transgenic mice on a murine PrP knockout background. The absolute species barrier between the infectious agent of TME and mice was therefore broken. Following TME and 79A infection of mice carrying both mink and murine PrPC, only proteinase-resistant PrP homologous to the incoming agent was detectable. The presence of the murine PrPC prolonged the incubation time of TME substantially.

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.

Transgenic Mice

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

Export Citation Format

Share Document