Unbiased modifier screen reveals that signal strength determines the regulatory role murine TLR9 plays in autoantibody production.

ABSTRACT: The autoimmune disease systemic lupus erythematosus has a complex environmental and multifactorial genetic basis. Genome-wide association studies have recently identified numerous disease-associated polymorphisms, but it remains unclear in which cells and during which step of pathogenesis specific polymorphisms interact to cause disease. Using a mouse model in which the same activating mutation (CD45E613R) causes distinct genetic background-dependent disease phenotypes, we performed a screen for genetic modifiers of autoreactivity between anti-nuclear Ab (ANA)-resistant CD45E613R.B6 and ANA-permissive CD45E613R.BALB/c mice. Within a novel autoreactivity-associated locus on chromosome 9, we identify a putative modifier, TLR9. Validating a role for TLR9 in modifying autoreactivity in the con

SUBMITTER: Mills RE 

PROVIDER: S-EPMC4503364 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature