Gene knockout animal models

1998 ◽  
pp. 143-162
Author(s):  
Bonnie Burgess-Beusse ◽  
Humberto E. Soriano ◽  
Gretchen J. Darlington
2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Georgios F. Hadjigeorgiou ◽  
Ranjodh Singh ◽  
Efthimios Dardiotis ◽  
Konstantinos Paterakis ◽  
Georgios M. Hadjigeorgiou ◽  
...  

1999 ◽  
Vol 82 (08) ◽  
pp. 865-869 ◽  
Author(s):  
Thomas Sato

IntroductionThe vascular system is one of the first organ systems to develop in our bodies. Normal development and maturation of the physiological functions of almost all of the other organs are critically dependent on the accurate and tightly controlled establishment of the vascular system. Our understanding of the mechanisms underlying the formation of the vascular system during development is still in its infancy. With further understanding of these mechanisms, we may eventually be able to correct the abnormal development and the malfunctioning of many organs by therapeutically modulating the morphology and/or physiological function of the vascular system.Our further understanding of the vascular development can, in part, be achieved by discovering the molecules that play critical roles in this process. We could also achieve this goal by learning more about the functions of previously identified molecules in the vascular system. Discovery of new processes underlying the development of the vascular system will also contribute to further understanding of these molecular mechanisms.Recent advances, using the whole genome approach, have resulted in a flood of new information. This trend will continue, and fortunately, a number of molecular reagents will become available. Therefore, the field will likely experience an exponential growth in terms of novel biological insights and discovering the mechanisms of vascular system development.Occasionally, reductionistic approaches help to systematically address a number of biological problems, including the problems associated with vascular system development. One such approach is to choose an organism that allows us to systematically address these biological questions. The choice of animal models that are well-suited for the study of a particular question has led to a large number of discoveries. To address questions in vascular system development, current research has focused on animal models, including fish, frog, bird, and mouse, and also studies involving humans. It is also worthwhile to note that the branching morphogenesis of the fly trachea system has been utilized to address fundamental questions of vascular morphogenesis.This chapter will summarize the genomic manipulation of the murine vascular system to address questions regarding vascular development. In addition, the advances that have been made in this field using such methods will be summarized.


2004 ◽  
Vol 84 (1) ◽  
pp. 87-136 ◽  
Author(s):  
M. A. LYNCH

Lynch, MA. Long-Term Potentiation and Memory. Physiol Rev 84: 87–136, 2004; 10.1152/physrev.00014.2003.—One of the most significant challenges in neuroscience is to identify the cellular and molecular processes that underlie learning and memory formation. The past decade has seen remarkable progress in understanding changes that accompany certain forms of acquisition and recall, particularly those forms which require activation of afferent pathways in the hippocampus. This progress can be attributed to a number of factors including well-characterized animal models, well-defined probes for analysis of cell signaling events and changes in gene transcription, and technology which has allowed gene knockout and overexpression in cells and animals. Of the several animal models used in identifying the changes which accompany plasticity in synaptic connections, long-term potentiation (LTP) has received most attention, and although it is not yet clear whether the changes that underlie maintenance of LTP also underlie memory consolidation, significant advances have been made in understanding cell signaling events that contribute to this form of synaptic plasticity. In this review, emphasis is focused on analysis of changes that occur after learning, especially spatial learning, and LTP and the value of assessing these changes in parallel is discussed. The effect of different stressors on spatial learning/memory and LTP is emphasized, and the review concludes with a brief analysis of the contribution of studies, in which transgenic animals were used, to the literature on memory/learning and LTP.


2002 ◽  
Vol 11 (3) ◽  
pp. 115-132 ◽  
Author(s):  
Ernesto Bockamp ◽  
Marko Maringer ◽  
Christian Spangenberg ◽  
Stephan Fees ◽  
Stuart Fraser ◽  
...  

The ability to engineer the mouse genome has profoundly transformed biomedical research. During the last decade, conventional transgenic and gene knockout technologies have become invaluable experimental tools for modeling genetic disorders, assigning functions to genes, evaluating drugs and toxins, and by and large helping to answer fundamental questions in basic and applied research. In addition, the growing demand for more sophisticated murine models has also become increasingly evident. Good state-of-principle knowledge about the enormous potential of second-generation conditional mouse technology will be beneficial for any researcher interested in using these experimental tools. In this review we will focus on practice, pivotal principles, and progress in the rapidly expanding area of conditional mouse technology. The review will also present an internet compilation of available tetracycline-inducible mouse models as tools for biomedical research ( http://www.zmg.uni-mainz.de/tetmouse/ ).


2004 ◽  
Vol 286 (3) ◽  
pp. C465-C474 ◽  
Author(s):  
A. S. Verkman

Drug discovery and development is generally done in the commercial rather than the academic realm. Drug discovery involves target discovery and validation, lead identification by high-throughput screening, and lead optimization by medicinal chemistry. Follow-up preclinical evaluation includes analysis in animal models of compound efficacy and pharmacology (ADME: administration, distribution, metabolism, elimination) and studies of toxicology, specificity, and drug interactions. Notwithstanding the high-cost, labor-intensive, and non-hypothesis-driven aspects of drug discovery, the academic setting has a unique and expanding niche in this important area of investigation. For example, academic drug discovery can focus on targets of limited commercial value, such as third-world and rare diseases, and on the development of research reagents such as high-affinity inhibitors for pharmacological “gene knockout” in animal models (“chemical genetics”). This review describes the practical aspects of the preclinical drug discovery process for academic investigators. The discovery of small molecule inhibitors and activators of the cystic fibrosis transmembrane conductance regulator is presented as an example of an academic drug discovery program that has yielded new compounds for physiology research and clinical development.


Author(s):  
Yun Feng ◽  
Xueyin Li ◽  
Xi Chen ◽  
Mengling Zhao ◽  
Qian Wang ◽  
...  

IntroductionThe mechanisms underlying the pathogenesis of recurrent pregnancy loss (RPL) and the effective approaches to treat this disease still remain vague and absent. Proteinases of ADAMTS family play important roles in embryonic growth and development. Our previous study suggest a role of ADAMTS13 during pregnancy. Current Study was to determine the expression of ADAMTS13 in human endometrium and its association with RPL.Material and methodsThe spatiotemporal expression of ADAMTS13 in human endometrium was examined by immunohistochemistry. real-time PCR sand western blot were then employed to determine the mRNA and protein expression levels of ADAMTS13 in human endometrium. Proteolytic cleavage of FRETS-VWF73 were performed to determine the activity of ADAMTS13 in plasma and that secreted by human endometrium. ELISA was carried out to measure plasma VWF antigen.ResultsWe show that proteolytically active ADAMTS13 is expressed in human endometrium throughout the menstrual cycle and pregnancy. The decidual expression levels of mRNA and protein in women with RPL were significantly lower compared with women with uncomplicated pregnancies (P<0.01, P<0.05, respectively). Furthermore, significantly reduced plasma ADAMTS13 activity (median [range] 69.09 [65.2–93.7]% versus 93.62 [88.1–115.6]%, P<0.001) and elevated plasma VWF antigen levels (median [range] of 125.5 [54.2–262.8]% versus 91.9[80.4–138.7]%, P < 0.01) were detected in RPL patients compared with the control group.ConclusionsThese findings suggest that ADAMTS13 may play a role in embryo implantation and the pathogenesis of recurrent pregnancy loss. Further investigation on ADAMTS13 gene knockout animal models is necessary for understanding the molecular mechanisms of the biological roles of ADAMTS13 during gestation.


2018 ◽  
Vol 315 (3) ◽  
pp. F628-F636 ◽  
Author(s):  
Lei Wang ◽  
Ximing Wang ◽  
Shan Jiang ◽  
Jin Wei ◽  
Jacentha Buggs ◽  
...  

Animal models of kidney transplantation (KTX) are widely used in studying immune response of hosts to implanted grafts. Additionally, KTX can be used in generating kidney-specific knockout animal models by transplantation of kidneys from donors with global knockout of a gene to wild-type recipients or vice versa. Dual-kidney transplantation (DKT) provides a more physiological environment for recipients than single-kidney transplantation (SKT). However, DKT in mice is rare due to technical challenges. In this study, we successfully performed DKT in mice and compared the hemodynamic response and graft function with SKT. The surgical time, complications, and survival rate of DKT were not significantly different from SKT, where survival rates were above 85%. Mice with DKT showed less injury and quicker recovery with lower plasma creatinine (Pcr) and higher glomerular filtration rate (GFR) than SKT mice (Pcr = 0.34 and 0.17 mg/dl in DKT vs. 0.50 and 0.36 mg/dl in SKT at 1 and 3 days, respectively; GFR = 215 and 131 µl/min for DKT and SKT, respectively). In addition, the DKT exhibited better renal functional reserve and long-term outcome of renal graft function than SKT based on the response to acute volume expansion. In conclusion, we have successfully generated a mouse DKT model. The hemodynamic responses of DKT better mimic physiological situations with less kidney injury and better recovery than SKT because of reduced confounding factors such as single nephron hyperfiltration. We anticipate DKT in mice will provide an additional tool for evaluation of renal significance in physiology and disease.


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