title: Neural-specific ablation of the scaffold protein JSAP1 in mice causes neonatal death.
abstract: We previously identified c-Jun NH(2)-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.
authors.affiliation: Division of Molecular Cell Signaling, Department of Molecular and Cellular Biology, Cancer Research Institute, Kanazawa University, Ishikawa 920-0934, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Iwanaga
authors.forename: Tokiharu
authors.initials: T
authors.lastname: Sato
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugihara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirao
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.forename: Katsuji
authors.initials: K
authors.lastname: Yoshioka
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology*; D016923:Cell Death / Q000235:genetics; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D009474:Neurons / Q000502:physiology*; D011804:Quinolines / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C403619:Mapk8ip3 protein, mouse; D009419:Nerve Tissue Proteins; D011804:Quinolines; C495966:TOTO-3 compound; D013844:Thiazoles; D049452:Green Fluorescent Proteins