Development of Transgenic Mouse Models for the Study of Human Olfactory Dysfunction

2005 ◽  
Vol 19 (3) ◽  
pp. 229-235 ◽  
Author(s):  
Andrew P. Lane ◽  
Haiqing Zhao ◽  
Randall R. Reed

Background Olfactory loss is a significant health problem that remains incompletely understood. The development of suitable animal models is essential to the progress of human olfactory loss research. Recent advancements in transgenic technology allow the creation of model systems to address causes of olfactory neuron dysfunction. Methods This review describes two transgenic mouse models with potential usefulness in the study of olfactory loss and highlights the molecular techniques that underlie the development of such systems. Results Genetic constructs generated using standard molecular biological techniques are introduced into mouse germ lines either by homologous recombination or by random integration. One construct (UbI7) places the olfactory receptor I7 under control of the olfactory marker protein promoter. The other two constructs (TI) act together to direct expression of cytokines in the olfactory epithelium, creating a novel approach to the study of inflammatory olfactory loss. Conclusions Powerful scientific tools now exist to develop animal models useful to the study of human olfactory disease. Transgenic olfactory neurons from the UbI7 mouse strain will respond to known odorants, facilitating experiments that examine in vitro modulation of olfactory neuron function. The ability to express specific genes in the olfactory mucosa of the TI mouse has great potential in elucidating the role of cytokines in the development of olfactory dysfunction in vivo.

2000 ◽  
Vol 8 (4) ◽  
pp. 1-8 ◽  
Author(s):  
Hao Ding ◽  
Andras Nagy ◽  
David H. Gutmann ◽  
Abhijit Guha

Despite tremendous technical improvements in neuroimaging and neurosurgery, the prognosis for patients with malignant astrocytoma remains devastating because of the underlying biology and growth characteristics of the tumor. However, our understanding of the molecular bases of these tumors has greatly increased due to study findings involving operative specimens, astrocytoma predisposing human syndromes, teratogen-induced animal and established human astrocytoma cell lines, and more recently transgenic mouse models. Appropriate small-animal models of spontaneously occurring astrocytomas, which replicate the growth and molecular characteristics found in human tumors, are essential to test the relevance and interactions of these molecular aberrations. In addition, it is hoped that relevant molecular targets will eventually be therapeutically exploited to improve patient outcomes. Appropriate animal models are also essential for testing these novel biological therapies, before they are brought to the clinic, requiring a large investment of time and money. In this paper, various astrocytoma models are discussed, with emphasis on transgenic mouse models that are of great interest to laboratory investigators.


2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Oliver Wirths ◽  
Thomas A. Bayer

Since their initial generation in the mid 1990s, transgenic mouse models of Alzheimers's disease (AD) have been proven to be valuable model systems which are indispensable for modern AD research. Whereas most of these models are characterized by extensive amyloid plaque pathology, inflammatory changes and often behavioral deficits, modeling of neuron loss was much less successful. The present paper discusses the current achievements of modeling neuron loss in transgenic mouse models based on APP/Aβand Tau overexpression and provides an overview of currently available AD mouse models showing these pathological alterations.


Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 5952-5957 ◽  
Author(s):  
I. Torres-Aleman

It is lay knowledge now that Alzheimer’s dementia (AD) is one of the most devastating diseases afflicting our societies. A major thrust in search for a cure has relied in the development of animal models of the disease. Thanks to progress in the genetics of the rare inherited forms of AD, various transgenic mouse models harboring human mutated proteins were developed, yielding very significant advancements in the understanding of pathological pathways. Although these models led to testing many different new therapies, none of the preclinical successes have translated yet into much needed therapeutic improvements. Further insight into the metabolic disturbances that are probably associated with the onset of the disease may also rely on new animal models of AD involving insulin/IGF-I signaling that could mimic the far most common sporadic forms of AD associated with old age. Combination of models of familial AD that develop severe amyloidosis with those displaying defects in insulin/IGF-I signaling may help clarify the link between putative initial metabolic disturbances and mechanisms of pathological progression.


1998 ◽  
Vol 165 (1) ◽  
pp. 47-61 ◽  
Author(s):  
Noelle Sevilir Williams ◽  
Jennifer Klem ◽  
Igor J. Puzanov ◽  
P. V. Sivakumar ◽  
John D. Schatzle ◽  
...  

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