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Research at OU


73  Asakura, Y.*1; Hirohashi, T.*1; Kikuchi, S.*1; Belcher, S.; Osborne, E.; Yano, S.*2; Terashima, I.*2; Barkan, A.; Nakai, M.*1
*1(Institute for Protein Research) *2(Graduate School of Science)
Maize Mutants Lacking Chloroplast FtsY Exhibit Pleiotropic Defects in the Biogenesis of Thylakoid Membranes
The Plant Cell, 16, 201-214 (2004)

74 Azukizawa, H.*1; Kosaka, H.*1; Sano, S.*1; Heath, W.R.; Takahashi, I.*1; Gao, X.H.; Sumikawa, Y.*1; Okabe, M.*2; Yoshikawa, K.*1; Itami, S.*1
*1(Graduate School of Medicine) *2(Genome Information Research Center)
Induction of T-cell-mediated Skin Disease Specific for Antigen Transgenically Expressed in Keratinocytes
The European Journal of Immunology, 33, 1879-1888 (2003)

Using transgenic mice, K5-mOVA, expressing ovalbumin (OVA) specifically in the epidermal keratinocytes, we have demonstrated that skin-derived self-antigens were presented to cytotoxic T cells (OT-I) by bone marrow-derived cells through cross-priming. Transferred OT-I cells targeted the skin of K5-mOVA mice, resulting in development of skin disease mimicking toxic epidermal necrolysis (TEN). We have concluded that our system provides a powerful model for autoimmune skin diseases and will aid understanding of the pathomechanism of drug eruption, viral exanthema, and graft-versus-host disease.

75 Chiba, T.; Hagihara, Y.; Higurashi, T.; Hasegawa, K.; Naiki, H.; Goto, Y.
(Institute for Protein Research)
Amyloid Fibril Formation in the Context of Full-length Protein
The Journal of Biological Chemistry, 278, 47016-47024 (2003)

Dialysis-related amyloidosis, which occurs in the patients receiving a long-term hemodialysis with high frequency, accompanies the deposition of amyloid fibrils composed of β2-microglobulin. To understand the mechanism of amyloid fibril formation, we studied the fibril formation of various mutants in which Pro was introduced to each of the seven beta strands. The results revealed that stability of the amyloid fibrils is a key factor determining the amyloidogenic potential of the proteins.

76 Hashimoto, K.*1; Shimizu, K.*2; Nakashima, N.; Sugino, A.*1
*1(Graduate School of Frontier Biosciences) *2(Radioisotope Research Center )
Fidelity of DNA Polymerase d Holoenzyme from Saccharomyces cerevisiae: The Sliding Clamp Proliferating Cell Nuclear Antigen Decreases Its Fidelity
Biochemistry, 42, 14207-14213 (2003)

DNA polymerases δ and e are the two major replicative polymerases in the budding yeast. The fidelity of pol δ is influenced by its 3'-5'proofreading exonuclease activity, which corrects misinsertion errors. We measured the fidelity of pol δ, and our results support the conclusion that the intrinsic fidelity of pol δ is low and that this is due primarily to the inherent fidelity of its DNA synthesis activity but only to a small extent on its 3'-5' exonuclease activity.

77 Hidaka, O.*1; Yanagi, M.*2; Takada, K.*2
*1(Dental Hospital) *2(Graduate School of Dentistry)
Changes in Masseteric Hemodynamics Time-related to Mental Stress
Journal of Dental Research, 83, 185-190 (2004)

This is the first confirmation of the temporal relationship between the finger sweat expulsion elicited by mental stress and the hemodynamic and electromyographic changes in the masseter muscle, a jaw-closing muscle. Masseteric hemodynamic changes were closely time-related to mental stress, whereas the EMG activity was not. These results suggest that mental stress induces hemodynamic changes that are not associated with EMG activity in the masseter muscle of healthy adults.

78 Horie, K.*1,2; Yusa, K.*2; Yae, K.*2; Odajima, J.*2; Fischer, S.E.J.; Keng, V.W.*2; Hayakawa, T.*2; Mizuno, S.*2; Kondoh, G.*2; Ijiri, T.; Matsuda, Y.; Plasterk, R.H.A.; Takeda, J.*1,2
*1(Center for Advanced Science and Innovation), *2(Graduate School of Medicine)
Characterization of Sleeping Beauty Transposition and Its Application to Genetic Screening in Mice
Molecular and Cellular Biology, 23, 9189-9207 (2003)

Mutant mice play a pivotal role in determining the function of genes. In this study, we conducted gene trap in mouse germline using a recently developed transposon, Sleeping Beauty (SB), and demonstrated that the SB transposon can be utilized for rapid generation of mutant mice. This is the first report of a large-scale generation of mutant mice using transposon system. Our results indicate that the SB transposon is a powerful tool for gene function study in the postgenomic era.

79 Kamada, Y.
(Graduate School of Medicine)
Enhanced Carbon Tetrachloride-Induced Liver Fibrosis in Mice Lacking Adiponectin
Gastroenterology, 125, 1796-1807 (2003)

Obesity is one of the risk factors for liver fibrosis in which plasma adiponectin levels are decreased. Adiponectin is an adipocytokine which we found in 1996. Here, we elucidated that adiponectin attenuates carbon tetrachloride-induced liver fibrosis in mice. We also found that adiponectin suppresses the proliferation and migration of hepatic stellate cells (HSCs) which play central roles in liver fibrosis. The findings indicate that adiponectin attenuates liver fibrosis and could be a novel approach in its prevention.

80 Kang, Y.; Notomi, T.; Saito, M.; Zhang, W.; Shigemoto, R.
(Graduate School of Dentistry)
Bidirectional Interactions between H-Channels and Na+ -K+ Pumps in Mesencephalic Trigeminal Neurons
The Journal of Neuroscience, 24, 3694-3702 (2004)

The Na+-K+ pump current and the h-current flowing through hyperpolarization-activated channels (h-channels) participate in generating the resting potential. These two currents are thought to be produced independently. We show here that the bidirectional interactions between Na+-K+ pumps and h-channels are likely to be mediated by Na+ microdomain in mesencephalic trigeminal neurons.

81 Konishi, A.*1; Shimizu, S.*1; Hirota, J.*2; Takao, T.*2; Fan, Y.; Matsuoka, Y.*3; Zhang, L.*1; Yoneda, Y.*3; Fujii, Y.; Skoultchi, A.I.; Tsujimoto, Y.*1
*1(Graduate School of Medicine) *2(Institute for Protein Research) *3(Graduate School of Frontier Biosceinces)
Involvement of Histone H1.2 in Apoptosis Induced by DNA Double-Strand Breaks
CELL, 114, 673-688 (2003)

82 Lee, S.J.*1; Sekimoto, T.*2; Yamashita, E.*1; Nagoshi, E.*2; Nakagawa, A.*1; Imamoto, N.; Yoahimura, M.*1; Sakai, H.*1; Chong, K.T.*1; Tsukihara, T.*1; Yoneda, Y.*3
*1(Institute for Protein Research) *2(Graduate School of Medicine) *3(Graduate School of Frontier Biosciences)
The Structure of Importin-β Bound to SREBP-2: Nuclear Import of a Transcription Factor
Science, 302, 1571-1575 (2003)
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