Neural-specific ablation of the scaffold protein JSAP1 in mice causes neonatal death

Asuka Iwanaga, Tokiharu Sato, Kazushi Sugihara, Atsushi Hirao, Nobuyuki Takakura, Hiroshi Okamoto, Masahide Asano, Katsuji Yoshioka

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We previously identified c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3) as a scaffolding factor for JNK intracellular signaling pathways. Targeted gene-disruption studies have shown that JSAP1-null mice are unable to breathe and die shortly after birth. Although neural defects might be responsible for their death, there has been no convincing evidence for this. Here we first generated genetically engineered mice carrying a loxP-flanked (floxed) jsap1 gene. To evaluate the validity of this deletion as a jsap1 conditional knockout (KO), we created mice in which the same exon was deleted in all cell lineages, and compared their phenotypes with those of the jsap1 conventional KO mice reported previously. The two KO lines showed indistinguishable phenotypes, i.e., neonatal death and morphological defects in the telencephalon, indicating that the conditional deletion was a true null mutation. We then introduced the floxed jsap1 deletion mutant specifically into the neural lineage, and found that the jsap1 conditional KO mice showed essentially the same phenotypes as the JSAP1-null mice. These results strongly suggest that the neonatal death of jsap1-deficient mice is caused by defects in the nervous system.

Original languageEnglish
Pages (from-to)43-48
Number of pages6
JournalNeuroscience Letters
Volume429
Issue number1
DOIs
Publication statusPublished - 2007 Dec 11

Keywords

  • Conditional knockout mouse
  • MAP kinase
  • Signal transduction

ASJC Scopus subject areas

  • Neuroscience(all)

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    Iwanaga, A., Sato, T., Sugihara, K., Hirao, A., Takakura, N., Okamoto, H., Asano, M., & Yoshioka, K. (2007). Neural-specific ablation of the scaffold protein JSAP1 in mice causes neonatal death. Neuroscience Letters, 429(1), 43-48. https://doi.org/10.1016/j.neulet.2007.09.057