著者

Fujikawa Keiko Iwata Takeshi Inoue Kaoru Akahori Masakazu Kadotani Hanako Fukaya Masahiro Watanabe Masahiko Chang Qing Barnett Edward M. Swat Wojciech

出版者

Public Library of Science

雑誌

PLoS ONE (ISSN:19326203)

巻号頁・発行日

vol.5, no.2, pp.e9050, 2010-02-04

被引用文献数

42

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Background: Glaucoma is a leading cause of blindness worldwide. Nonetheless, the mechanism of its pathogenesis has not been well-elucidated, particularly at the molecular level, because of insufficient availability of experimental genetic animal models. Methodology/Principal Findings: Here we demonstrate that deficiency of Vav2 and Vav3, guanine nucleotides exchange factors for Rho guanosine triphosphatases, leads to an ocular phenotype similar to human glaucoma. Vav2/Vav3-deficient mice, and to a lesser degree Vav2-deficient mice, show early onset of iridocorneal angle changes and elevated intraocular pressure, with subsequent selective loss of retinal ganglion cells and optic nerve head cupping, which are the hallmarks of glaucoma. The expression of Vav2 and Vav3 tissues was demonstrated in the iridocorneal angle and retina in both mouse and human eyes. In addition, a genome-wide association study screening glaucoma susceptibility loci using single nucleotide polymorphisms analysis identified VAV2 and VAV3 as candidates for associated genes in Japanese open-angle glaucoma patients. Conclusions/Significance: Vav2/Vav3-deficient mice should serve not only as a useful murine model of spontaneous glaucoma, but may also provide a valuable tool in understanding of the pathogenesis of glaucoma in humans, particularly the determinants of altered aqueous outflow and subsequent elevated intraocular pressure.

著者

Ichikawa Ryoichi Yamasaki Miwako Miyazaki Taisuke Konno Kohtarou Hashimoto Kouichi Tatsumi Haruyuki Inoue Yoshiro Kano Masanobu Watanabe Masahiko

出版者

Society for Neuroscience

雑誌

The Journal of neuroscience : the official journal of the Society for Neuroscience (ISSN:15292401)

巻号頁・発行日

vol.31, no.47, pp.16916-16927, 2011-11-23

被引用文献数

50

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In early postnatal development, perisomatic innervation of cerebellar Purkinje cells (PCs) switches from glutamatergic climbing fibers (CFs) to GABAergic basket cell fibers (BFs). Here we examined the switching process in C57BL/6 mice. At postnatal day 7 (P7), most perisomatic synapses were formed by CFs on to somatic spines. The density of CF-spine synapses peaked at P9, when pericellular nest around PCs by CFs was most developed, and CF-spine synapses constituted 88% of the total perisomatic synapses. Thereafter, CF-spine synapses dropped to 63% at P12, 6% at P15, and <1% at P20, whereas BF synapses increased reciprocally. During the switching period, a substantial number of BF synapses existed as BF-spine synapses (37% of the total perisomatic synapses at P15), and free spines surrounded by BFs or Bergmann glia also emerged. By P20, BF-spine synapses and free spines virtually disappeared, and BF-soma synapses became predominant (88%), thus attaining the adult pattern of perisomatic innervation. Parallel with the presynaptic switching, postsynaptic receptor phenotype also switched from glutamatergic to GABAergic. In the active switching period, particularly at P12, fragmental clusters of AMPA-type glutamate receptor were juxtaposed with those of GABA(A) receptor. When examined with serial ultrathin sections, immunogold labeling for glutamate and GABA(A) receptors was often clustered beneath single BF terminals. These results suggest that a considerable fraction of somatic spines is succeeded from CFs to BFs and Bergmann glia in the early postnatal period, and that the switching of postsynaptic receptor phenotypes mainly proceeds under the coverage of BF terminals.

著者

Watanabe Masahiko Hirai Yoshio

出版者

日本応用動物昆虫学会

雑誌

Applied entomology and zoology (ISSN:00036862)

巻号頁・発行日

vol.39, no.2, pp.249-254, 2004-05-25

参考文献数

14

被引用文献数

1 22

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Host-use pattern for overwintering and reproduction of the ragweed beetle, Ophraella communa LeSage, was examined in Tsukuba, Japan. Many adults of both sexes were found overwintering inside the rolled parts of dead leaves of Xanthium canadense in November. These adults had already accumulated triacylglycerol as energy reserves, and were able to survive the winter and to reproduce in the spring. No eggs and larvae were found on X. canadense throughout the observation period, although overwintered adults were temporarily found in May. In contrast, reproduction occurs on Ambrosia artemisiifolia and A. trifida in late April. These results suggest that O. communa adults mainly use dead leaves of X. canadense as an overwintering shelter in Tsukuba, while they reproduce only on A. artemisiifolia and A. trifida in the spring. Such a seasonal migration between host plants may be important for the survival strategy.