Single gene effects in mouse models of host: pathogen interactions.

Abstract:

:Inbred mouse strains have been known for many years to vary in their degree of susceptibility to different types of infectious diseases. The genetic basis of these interstrain differences is sometimes simple but often complex. In a few cases, positional cloning has been used successfully to identify single gene effects. The natural resistance-associated macrophage protein 1 (Nramp1) gene (Slc11a1) codes for a metal transporter active at the phagosomal membrane of macrophages, and Nramp1 mutations cause susceptibility to Mycobacterium, Salmonella, and Leishmania. Furthermore, recent advances in gene transfer technologies in transgenic mice have enabled the functional dissection of gene effects mapping to complex, repeated parts of the genome, such as the Lgn1 locus, causing susceptibility to Legionella pneumophila in macrophages. Finally, complex traits such as the genetically determined susceptibility to malaria can sometimes be broken down into multiple single gene effects. One such example is the case of pyruvate kinase, where a loss-of-function mutation was recently shown by our group to be protective against blood-stage infection with Plasmodium chabaudi. In all three cases reviewed, the characterization of the noted gene effect(s) has shed considerable light on the pathophysiology of the infection, including host response mechanisms.

journal_name

J Leukoc Biol

authors

Fortier A,Min-Oo G,Forbes J,Lam-Yuk-Tseung S,Gros P

doi

10.1189/jlb.1004616

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

868-77

issue

6

eissn

0741-5400

issn

1938-3673

pii

jlb.1004616

journal_volume

77

pub_type

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