Abstract：
:A simple method of manipulating neuronal gene expression would greatly facilitate the design of experiments to increase our understanding of and ability to treat diseases of the CNS. However, until recently most transfection methods could only deliver DNA into dividing cells and it was only possible to manipulate neuronal gene expression through the production of transgenic animals. The development of powerful new viral-based gene transfer systems has generated a great deal of research interest in the field of therapeutic gene transfer during the last decade. One of the most powerful and versatile gene delivery systems currently available is the recombinant adenovirus (Ad) vector. These vectors can transfect postmitotic neurons in the CNS, but have not yet been fully evaluated as CNS gene therapy vectors. Brattleboro rats contain a point mutation in the arginine vasopressin (AVP) gene that results in a pathological phenotype characterized by a lack of circulating AVP. This decrease in AVP in turn causes the characteristics signs of diabetes insipidus, with the production of large volumes of dilute urine and a compensatory drinking of large volumes of water (equivalent to the body weight of the rat per day). We have shown that injection of an Ad encoding the arginine vasopressin cDNA into the supraoptic nuclei of the hypothalamus results in the long-term reversal of this pathological phenotype. This was demonstrated by reduced daily water intake and micturition, as well as increased urine osmolality lasting 4 months. The highly characterized Brattleboro rat model of hypothalamic diabetes insipidus, therefore, provides the means to examine noninvasively the efficacy of viral and nonviral gene therapy strategies in the CNS.
journal_name
Front Neuroendocrinoljournal_title
Frontiers in neuroendocrinologyauthors
Geddes BJ,Harding TC,Lightman SL,Uney JBdoi
10.1006/frne.1999.0184subject
Has Abstractpub_date
1999-10-01 00:00:00pages
296-316issue
4eissn
0091-3022issn
1095-6808pii
S0091-3022(99)90184-Xjournal_volume
20pub_type
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