International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Poltorak A
The Scripps Research Institute

Co-Authors: Smirnova I, Hoebe K
Institutions: The Scripps Research Institute

Spontaneous mutations in classical laboratory inbred strains of mice have been extremely helpful for the analysis of immunologically relevant traits. However, their genetic polymorphism is rather limited. In order to increase the number of polymorphisms of natural origin, different species of Mus derived from wild progenitors can be used in studies of immune functions. In order to identify new genes that may be involved in innate immune response, we compared several inbred and wild-derived strains of mice in their response to various agonists of toll-like receptors (Tlr) family members. In MOLF/Ei, MSM/Ms, and Spretus/Ei strains we have observed a significant variability in responses to CpG, Poly I:C, as well as to LPS. MOLF/Ei and MSM/Ei mice are hypo-responsive to poly I:C. In addition, MOLF/Ei strain has extremely low response to CpG. TNF synthesis in Spretus/Ei mice in response to LPS is significantly elevated compared to all other strains. Genetic analysis of the backcross progeny showed that these phenotypes do not appear to be linked to any of Tlr loci in mouse genome, thus revealing a set of modifier genes that might be involved in innate response.

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