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  Susceptibility to Anthrax Lethal Toxin is Controlled by Three Linked Quantitative Trait Loci

McAllister, R. D., Singh, Y., du Bois, W. D., Potter, M., Boehm, T., Meeker, N. D., Fillmore, P. D., Anderson, L. M., Poynter, M. E., & Teuscher, C. (2003). Susceptibility to Anthrax Lethal Toxin is Controlled by Three Linked Quantitative Trait Loci. American Journal of Pathology, 163(5), 1735-1741. doi:10.1016/S0002-9440(10)63532-8.

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資料種別: 学術論文

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 作成者:
McAllister, Ryan D.1, 著者
Singh, Yogendra1, 著者
du Bois, Wendy D.1, 著者
Potter, Michael1, 著者
Boehm, Thomas2, 著者           
Meeker, Nathan D.1, 著者
Fillmore, P. D.1, 著者
Anderson, Lisa M.1, 著者
Poynter, Matthew E.1, 著者
Teuscher, Cory1, 著者
所属:
1External Organizations, ou_persistent22              
2Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243647              

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 要旨: Anthrax lethal toxin (LT) is the principal virulence factor associated with lethal pathologies following infection with Bacillus anthracis. Macrophages are the primary effector cells mediating lethality since macrophage-depleted mice are resistant to LT challenge. Recently, Ltxs1, the gene controlling differential susceptibility of murine macrophages to cytolysis following in vitro exposure to LT, was identified as Kif1c. To directly assess the in vivo role of Kif1c alleles in mortality, we studied a panel of interval-specific recombinant congenic lines carrying various segments of central chromosome 11 derived from LT-resistant DBA/2 mice on the LT-susceptible BALB/c background. The results of this study reveal that mortality is controlled by three linked quantitative trait loci (QTL): Ltxs1/Kif1c (42-43 cM), Ltxs2 (35-37 cM), and Ltxs3 (45-47 cM). The Ltxs3 interval encompasses Nos2, which is an attractive candidate gene for Ltxs3. In this regard, we demonstrate that selective, pharmacologically based inhibition of Nos2 activity in vivo partially overrides genetic resistance to LT and that Nos2 expression as determined by reverse transcription-polymerase chain reaction differs significantly between DBA/2 and BALB/c macrophages. Additionally, to recapitulate dominant resistance to mortality as seen in (BALB/c x DBA/2)F1 hybrids, DBA/2 alleles are required at all three QTL.

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言語: eng - English
 日付: 2003-11
 出版の状態: オンラインで出版済み
 ページ: -
 出版情報: -
 目次: -
 査読: 査読あり
 識別子(DOI, ISBNなど): ISI: 000186148200008
DOI: 10.1016/S0002-9440(10)63532-8
 学位: -

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出版物 1

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出版物名: American Journal of Pathology
  出版物の別名 : Am. J. Pathol.
種別: 学術雑誌
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出版社, 出版地: -
ページ: - 巻号: 163 (5) 通巻号: - 開始・終了ページ: 1735 - 1741 識別子(ISBN, ISSN, DOIなど): ISSN: 0002-9440