Use of antisense oligodeoxynucleotides to inhibit expression of glutamate transporter subtypes.
Antisense ODN are highly effective tools to selectively inhibit synthesis of glutamate transporter subtypes. They have been used to evaluate the biology of individual transporter subtypes in vivo and in vitro. Appropriate use of antisense ODN, however, requires a number of important controls to validate the specificity of their effects. Ultimately, the efficacy at inhibiting the synthesis of transporters proteins reflects several variables: the actual efficacy of the antisense to directly inhibit synthesis, the rate of degradation of the ODN, the rate of intracellular penetration of the ODN, the rate of new protein synthesis for the transporter subtype, and the actual penetration of the ODN into CNS tissue. The methods described in this chapter will help one to optimize each of these parameters.
Bristol
L A
LA
Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Rothstein
J D
JD
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001483:Base Sequence; D002151:Calorimetry; D002352:Carrier Proteins / Q000235:genetics; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D007263:Infusions, Parenteral; D020319:Oligodeoxyribonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism; D027981:Symporters
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D050491:Glutamate Plasma Membrane Transport Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D027981:Symporters; D018698:Glutamic Acid