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Publication : Immunotoxin-mediated conditional disruption of specific neurons in transgenic mice.

First Author  Kobayashi K Year  1995
Journal  Proc Natl Acad Sci U S A Volume  92
Issue  4 Pages  1132-6
PubMed ID  7862648 Mgi Jnum  J:338363
Mgi Id  MGI:7511876 Doi  10.1073/pnas.92.4.1132
Citation  Kobayashi K, et al. (1995) Immunotoxin-mediated conditional disruption of specific neurons in transgenic mice. Proc Natl Acad Sci U S A 92(4):1132-6
abstractText  We have developed a transgenic approach, termed immunotoxin-mediated cell targeting (IMCT), to ablate conditionally selective neurons in the brain with the cytotoxic activity of immunotoxins. Transgenic mice were created that express the human interleukin 2 receptor alpha subunit (IL-2R alpha) under the control of the dopamine beta-hydroxylase (DBH) gene promoter. The animals were treated intracerebroventricularly with a recombinant immunotoxin, anti-Tac(Fv)-PE40, which selectively kills animal cells bearing human IL-2R alpha. The immunotoxin caused a characteristic behavioral abnormality only in the transgenic mice. This was accompanied by a dramatic loss of DBH-containing neurons and a significant decrease in DBH activity and norepinephrine levels in various regions of the brain. IMCT should provide a general technique to create animal models of human neurodegenerative disorders by targeting neurons or other cell types.
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