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. 1995 Feb 14;92(4):1132–1136. doi: 10.1073/pnas.92.4.1132

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

K Kobayashi 1, S Morita 1, H Sawada 1, T Mizuguchi 1, K Yamada 1, I Nagatsu 1, K Fujita 1, R J Kreitman 1, I Pastan 1, T Nagatsu 1
PMCID: PMC42652  PMID: 7862648

Abstract

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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Selected References

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