scholarly journals A Natural Animal Model System of Craniofacial Anomalies: The Blind Mexican Cavefish

2018 ◽  
Vol 303 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Joshua B. Gross ◽  
Amanda K. Powers
Keyword(s):  
Animal Model ◽  
Model System ◽  
Craniofacial Anomalies

Membrane-associated microtubular areays induced in proximal myelinated processes of dorsal root ganglia by large doses of vitamin B6

1986 ◽  
Vol 44 ◽  
pp. 368-369
Author(s):  
V.J. Montpetit ◽  
S. Dancea ◽  
L. Tryphonas ◽  
D.F. Clapin
Keyword(s):  
Animal Model ◽  
Endoplasmic Reticulum ◽  
Dorsal Root Ganglia ◽  
Rough Endoplasmic Reticulum ◽  
Dorsal Root ◽  
Vitamin B6 ◽  
Morphological Changes ◽  
Model System ◽  
Sensory Nerves ◽  
Peripheral Sensory

Very large doses of pyridoxine (vitamin B6) are neurotoxic in humans, selectively affecting the peripheral sensory nerves. We have undertaken a study of the morphological and biochemical aspects of pyridoxine neurotoxicity in an animal model system. Early morphological changes in dorsal root ganglia (DRG) associated with pyridoxine megadoses include proliferation of neurofilaments, ribosomes, rough endoplasmic reticulum, and Golgi complexes. We present in this report evidence of the formation of unique aggregates of microtubules and membranes in the proximal processes of DRG which are induced by high levels of pyridoxine.

Proteomic and PROTEOMEX profiling of mammary cancer progression in a HER-2/neu oncogene-driven animal model system

2011 ◽  
Vol 5 (3-4) ◽  
pp. 200-200
Author(s):  
Stefania Croci ◽  
Christian V. Recktenwald ◽  
Rudolf Lichtenfels ◽  
Giordano Nicoletti ◽  
Sven P. Dressler ◽  
...  
Keyword(s):  
Animal Model ◽  
Cancer Progression ◽  
Mammary Cancer ◽  
Model System ◽  
Her 2 ◽  
Neu Oncogene

scholarly journals Effects of an antiplatelet glycoprotein Ib antibody on hemostatic function in the guinea pig

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 690-694 ◽  
Author(s):  
BH Becker ◽  
JL Miller
Keyword(s):  
Animal Model ◽  
Platelet Count ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Bleeding Time ◽  
Model System ◽  
Platelet Counts ◽  
Equal Dose ◽  
Guinea Pig Model

Abstract Previous studies in the guinea pig model system have established a close structural homology between human and guinea pig glycoproteins Ib (GPIb) and IIb/IIIa (GPIIb/IIIa). Moreover, the murine monoclonal antibody (MoAb) PG-1, which recognizes GPIb in guinea pig platelets and megakaryocytes, exerted full inhibition on von Willebrand factor (vWF)- dependent platelet agglutination without inhibiting aggregation induced by ADP, collagen, or thrombin. The present research extends this animal model system to study of the effects on hemostatic function following the in vivo injection of MoAb PG-1 or its F(ab')2 fragments. A hind limb template bleeding time methodology was developed for use in guinea pigs. Normal bleeding time was determined to be 2.7 +/- 0.5 minutes (mean +/- SD), with an observed range of two to four minutes. Platelet counts in these same animals were 501 +/- 82 x 10(3)/microL. After intraperitoneal (IP) injection of busulfan, guinea pigs became increasingly thrombocytopenic. As long as the platelet count remained above approximately 150 x 10(3)/microL, the bleeding time was not more than five minutes; however, further decrease in the platelet count was accompanied by more marked prolongations of the bleeding time. For 14 to 72 hours after IP injection of 1.3 mg/kg intact PG-1 MoAb, a hemorrhagic state was produced with a bleeding time greater than 20 minutes. The platelet count concurrently decreased to approximately 50% of its baseline value but could not be further decreased either by raising the initial PG-1 dosage tenfold or by administering a second, equal dose 24 hours after the initial injection. This finding may reflect a heterogeneity of circulating platelets with respect to GPIb, to Fc receptors, or to an interaction between them. After IP injection of 0.63 to 2.5 mg/kg PG-1 F(ab')2 fragment, platelet counts did not decrease more than 21% below baseline levels in a 72-hour period, and bleeding times never increased by more than one minute over baseline values. Nevertheless, platelets obtained from animals 24 hours after injection of 2.5 mg/kg PG-1 F(ab')2 showed full inhibition of agglutination induced by ristocetin. The response of these platelets to aggregation by asialo-vWF was also severely inhibited as compared with control platelets. PG-1 F(ab')2 produced no effect on aggregation induced by ADP. These studies show that virtually complete functional block of the vWF receptor by F(ab')2 fragments of the anti-GPIb MoAb PG- 1 is not sufficient to produce a hemorrhagic state in the guinea pig animal model system.

Lessons from Worm Dendritic Patterning

2019 ◽  
Vol 42 (1) ◽  
pp. 365-383 ◽  
Author(s):  
Sharon Inberg ◽  
Anna Meledin ◽  
Veronika Kravtsov ◽  
Yael Iosilevskii ◽  
Meital Oren-Suissa ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Animal Model ◽  
Light And Electron Microscopy ◽  
Dendritic Tree ◽  
Model System ◽  
Model Organisms ◽  
Structural Units ◽  
The Past ◽  
Structural And Functional Properties ◽  
Made In

The structural and functional properties of neurons have intrigued scientists since the pioneering work of Santiago Ramón y Cajal. Since then, emerging cutting-edge technologies, including light and electron microscopy, electrophysiology, biochemistry, optogenetics, and molecular biology, have dramatically increased our understanding of dendritic properties. This advancement was also facilitated by the establishment of different animal model organisms, from flies to mammals. Here we describe the emerging model system of a Caenorhabditis elegans polymodal neuron named PVD, whose dendritic tree follows a stereotypical structure characterized by repeating candelabra-like structural units. In the past decade, progress has been made in understanding PVD's functions, morphogenesis, regeneration, and aging, yet many questions still remain.

scholarly journals The V-ATPase V1 subunit A1 is required for rhodopsin anterograde trafficking in Drosophila

2018 ◽  
Vol 29 (13) ◽  
pp. 1640-1651 ◽  
Author(s):  
Haifang Zhao ◽  
Jing Wang ◽  
Tao Wang
Keyword(s):  
Animal Model ◽  
Endoplasmic Reticulum ◽  
Secretory Pathway ◽  
Photoreceptor Cell ◽  
Photoreceptor Cells ◽  
Secretory Vesicle ◽  
Light Sensitivity ◽  
Model System ◽  
Genetic Screen ◽  
Reduced Light

Synthesis and maturation of the light sensor, rhodopsin, are critical for the maintenance of light sensitivity and for photoreceptor homeostasis. In Drosophila, the main rhodopsin, Rh1, is synthesized in the endoplasmic reticulum and transported to the rhabdomere through the secretory pathway. In an unbiased genetic screen for factors involved in rhodopsin homeostasis, we identified mutations in vha68-1, which encodes the vacuolar proton-translocating ATPase (V-ATPase) catalytic subunit A isoform 1 of the V1 component. Loss of vha68-1 in photoreceptor cells disrupted post-Golgi anterograde trafficking of Rh1, reduced light sensitivity, increased secretory vesicle pH, and resulted in incomplete Rh1 deglycosylation. In addition, vha68-1 was required for activity-independent photoreceptor cell survival. Importantly, vha68-1 mutants exhibited phenotypes similar to those exhibited by mutations in the V0 component of V-ATPase, vha100-1. These data demonstrate that the V1 and V0 components of V-ATPase play key roles in post-Golgi trafficking of Rh1 and that Drosophila may represent an important animal model system for studying diseases associated with V-ATPase dysfunction.

Naturally-Occurring Antibodies to Human AAV In Sheep: A New Large Animal Model for Immune Aspects of AAV Gene Transfer.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3762-3762
Author(s):  
Joseph Tellez ◽  
Jonathan D. Finn ◽  
Nicholas Tschernia ◽  
Graca Almeida-Porada ◽  
Valder Arruda ◽  
...  
Keyword(s):  
Animal Model ◽  
Conflicts Of Interest ◽  
High Titer ◽  
Cell Epitope ◽  
Model System ◽  
Large Animal Model ◽  
Preclinical Model ◽  
Large Animal ◽  
Target Tissue ◽  
Naturally Occurring

Abstract Abstract 3762 AAV vectors have received a great deal of attention for clinical gene therapy (GT), since they transduce many mitotic and quiescent cells and mediate long-term transgene expression. Unfortunately, many of the serotypes of AAV commonly employed in GT procedures ubiquitously infect humans, generating pre-existing immunity against the AAV capsid proteins that precludes efficient transduction or induces CTL responses to the transduced target tissue. At present, highly successful animal studies have not translated into clinical success in humans, due, at least in part, to the paucity of animals which harbor endogenous antibodies which recognize and bind AAV-2 and other AAV serotypes for which humans are the natural host. Sheep have long been used as a model to study a broad range of disease states, and a high degree of clinical predictability has consistently been observed. We therefore examined whether sheep possess antibodies to AAV and could thus serve as a much-needed preclinical model system for evaluating AAV-based GT. ELISAs were performed on sera from a panel of 6 healthy Merino-Rambouillet sheep using AAV-1,-2,-5,-6,-8, -9 particles as the antigen. Our results demonstrate that sheep naturally harbor antibodies to all 6 AAV serotypes tested, yet the titers against the different serotypes varied greatly from sheep-to-sheep. While one sheep exhibited very high level (>2300ng/ml) IgG against all 6 AAV serotypes tested, others exhibited moderate/low (>350ng/ml) IgG against all 6 AAV serotypes, and still others exhibited moderate/low level IgG against only 3–4 of the tested serotypes. Despite these differences, all sheep harbored detectable antibodies to AAV 2, 5, & 8. A luciferase-based neutralizing antibody (NAB) assay was then performed on sera from 3 of the sheep exhibiting the highest titer IgG against AAV 2, 8, & 9 to assess the clinical significance of these antibodies in the context of AAV-based GT. All 3 animals harbored relatively high titer (1:100-1:316) NAB to AAV 2, but only 1 animal harbored significant NAB titers against AAV 8 & 9 (1:31, and 1:100, respectively). B cell epitope mapping of these 3 animals with a library of peptides derived from the capsids of AAV 2, 5, 8, and 9 revealed that each individual sheep harbored antibodies recognizing from 17 to 50 of the various capsid-derived peptides, some of which were common to all capsids, and some of which were unique to specific AAV serotypes. Importantly, many of the identified capsid epitopes have also been shown to be recognized by antibodies present in human patients with existing AAV immunity. To our knowledge, this is the first report of an animal disease model harboring naturally occurring functional antibodies to serotypes of human AAV commonly employed as GT vectors. The close parallels between human and sheep physiology, coupled with our recent re-establishment of sheep with severe hemophilia A with a null mutation in the FVIII gene and the presence of these antibodies, suggest that sheep may represent an ideal large animal model system in which to study GT in the context of pre-existing immunity to AAV, and to develop novel strategies for circumventing this immunologic barrier. Disclosures: No relevant conflicts of interest to declare.

Animal Model Systems for the Study of Alcohol Teratology

2005 ◽  
Vol 230 (6) ◽  
pp. 389-393 ◽  
Author(s):  
Timothy A. Cudd
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Basic Science ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Model System ◽  
Higher Order ◽  
Model Systems ◽  
Large Animal ◽  
Prenatal Alcohol

The incidence of fetal alcohol syndrome has not been declining even though alcohol has been established as a teratogen and significant efforts have been made to educate women not to abuse alcohol during pregnancy. In addition to further educational efforts, strategies to prevent or mitigate the damages of prenatal alcohol exposure are now under development. Animal models will play a significant role in the effort to develop these strategies. Because prenatal alcohol exposure causes damage by multiple mechanisms, depending on dose, pattern, and timing of exposure, and because no species of animal is the same as the human, the choice of which animal model to use is complicated. To choose the best animal model, it is necessary to consider the specific scientific question that is being addressed and which model system is best able to addressthe question. Animal models that are currently in use include nonhuman primates, rodents (rats, mice, guinea pigs), large animal models (pig and sheep), the chick, and simple animals, including fish, insects, and round worms. Each model system has strengths and weaknesses, depending on the question being addressed. Simple animal models are useful in exploring basic science questions that relate to molecular biology and genetics that cannot be explored in higher-order animals, whereas higher-order animal models are useful in studying complex behaviors and validating basic science findings in an animal that is more like the human. Substantial progress in this field will require the judicious use of multiple scientific approaches that use different animal model systems.

Animal Model System for Studying Virulence of and Host Response to Bacteroides fragilis

1990 ◽  
Vol 12 (Supplement_2) ◽  
pp. S169-S177 ◽  
Author(s):  
Andrew B. Onderdonk ◽  
Ronald L. Cisneros ◽  
Robert Finberg ◽  
Joseph H. Crabb ◽  
Dennis L. Kasper
Keyword(s):  
Animal Model ◽  
Host Response ◽  
Bacteroides Fragilis ◽  
Model System
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