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The genetic dissection of mycobacter...

Di Pietrantonio, Tania.

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The genetic dissection of mycobacterial infection.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	The genetic dissection of mycobacterial infection./
作者:	Di Pietrantonio, Tania.
面頁冊數:	222 p.
附註:	Source: Dissertation Abstracts International, Volume: 72-09, Section: B, page: .
Contained By:	Dissertation Abstracts International72-09B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR74420
ISBN:	9780494744208

The genetic dissection of mycobacterial infection.
Di Pietrantonio, Tania.

The genetic dissection of mycobacterial infection. - 222 p.

Source: Dissertation Abstracts International, Volume: 72-09, Section: B, page: .

Thesis (Ph.D.)--McGill University (Canada), 2011.

The host response to mycobacterial infection is highly variable. A role for host and bacterial factors in this variability is well established, although it is not known whether these factors act independently of each other or whether infection outcome results from a joint effect of host and pathogen. To address this question, the present thesis concurrently examined the effect of genetically controlled host and bacterial factors using a mouse model of infection. A panel of recombinant congenic (RC) mouse strains and their A/J and C57BL/6J inbred progenitors were infected with virulent Mycobacterium tuberculosis or the attenuated M. bovis Bacille Calmette Guerin (BCG) Russia and Pasteur strains. A joint effect of host and pathogen on the course of mycobacterial infection was observed at both the phenotypic and genetic level. In the A/J and C57BL/6Jmouse strains, pathogen-associated factors had a major impact on biological phenotypes (pulmonary replication, lung histopathology) as well as mechanistic phenotypes (pulmonary transcription of Ifng, Il12b, Il4 and chemokine genes) with the host genetic background modulating the magnitude of these responses. At the genetic level, a comparative analysis of the pulmonary and splenic counts of BCG Russia and BCG Pasteur in the RC strains revealed that mycobacterial infection is under the control of both generic and strain-specific genetic effects. A locus on chromosome 1 indistinguishable from Nramp1 controlled early BCG Pasteur and early and late BCG Russia infection in a spleen-specific manner. Loci impacting on the counts of BCG Russia but not BCG Pasteur were identified on chromosome 13 for the spleen and on chromosome 11 for the lung and spleen at the late phase of infection. M. tuberculosis infection was also under distinct genetic control in the RC strains, further demonstrating that genetic control of mycobacterial infection is adapted to the infecting mycobacterial strain. A strong genetic effect detected on chromosome 10 was linked with early death following M. tuberculosis infection. Analysis conditional on this locus identified a set of genetic control elements on chromosomes 2, 4, and 13. Together, these studies provide compelling evidence for strong specificity of the host response to the infecting pathogen.

ISBN: 9780494744208Subjects--Topical Terms:

1017730
Biology, Genetics.

The genetic dissection of mycobacterial infection.
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