کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10956757 | 1099446 | 2006 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A genetically modified mouse model probing the selective action of ifenprodil at the N-methyl-d-aspartate type 2B receptor
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A genetically modified mouse model probing the selective action of ifenprodil at the N-methyl-d-aspartate type 2B receptor A genetically modified mouse model probing the selective action of ifenprodil at the N-methyl-d-aspartate type 2B receptor](/preview/png/10956757.png)
چکیده انگلیسی
Selective antagonism of N-methyl-d-aspartate (NMDA) 2B subunit containing receptors has been suggested to have potential therapeutic application for multiple CNS disorders. The amino terminal NR2B residues 1 to 282 were found to be both necessary and sufficient for the binding and function of highly NR2B subunit specific antagonists like ifenprodil and CP-101,606. Using a genetic approach in mice, we successfully replaced the murine NR2B gene function by “knocking-in” (KI) a chimeric human NR2A/B cDNA containing the minimal domain abolishing ifenprodil binding into the endogenous NR2B locus. Patch-clamp recording from hippocampal cultures of the NR2B KI mice demonstrated that their NMDA receptors have reduced sensitivity to both ifenprodil and CP-101,606, as predicted, but also have a lower affinity for glycine. The NR2B KI mice exhibited normal locomotor activity making this ifenprodil-insensitive mouse model a valuable tool to test the specificity of NR2B selective antagonists in vivo.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Neuroscience - Volume 33, Issue 1, September 2006, Pages 47-56
Journal: Molecular and Cellular Neuroscience - Volume 33, Issue 1, September 2006, Pages 47-56
نویسندگان
Thomas W. Rosahl, Peter B. Wingrove, Verity Hunt, Rosa L. Fradley, Jason M.K. Lawrence, Robert P. Heavens, Patrick Treacey, Marcelo Usala, Alison Macaulay, Timothy P. Bonnert, Paul J. Whiting, Keith A. Wafford,