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

NEUROSCIENCE LETTERS

卷:429

Article

Iwanaga, Asuka¹  Sato, Tokiharu¹  Hirao, Atsushi²  Takakura, Nobuyuki³  Okamoto, Hiroshi⁴  Yoshioka, Katsuji¹ 

[1] Kanazawa Univ, Canc Res Inst, Dept Mol & Cellular Biol, Div Mol Cell Signaling, Kanazawa, Ishikawa 9200934, Japan

[2] Kanazawa Univ, Canc Res Inst, Ctr Canc & Stem Cell Res, Div Mol Genet, Kanazawa, Ishikawa 920, Japan

[3] Osaka Univ, Res Inst Microbial Dis, Dept Signa Transduct, Osaka, Japan

[4] Tohoku Univ, Grad Sch Med, Dept Adv Biol Sci Regenerat, Kotobiken Med Labs, Sendai, Miyagi 980, Japan

关键词: conditional knockout mouse;    MAP kinase;    signal transduction;   

DOI  :  10.1016/j.neulet.2007.09.057

来源: Elsevier

【 摘 要 】

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 jsapl 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 jsapl deletion mutant specifically into the neural lineage, and found that the jsapl 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. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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