Dataset Information

Influence of genetic variation on inducible gene expression in murine CD4+ splenocytes.

ABSTRACT: Because activation of the immune response is dependent on extensive changes in gene expression, it is likely that a major component of inter-individual variation in the immune response is ultimately mediated at the level of gene regulation. Here, we examine the influence of genetic variation on inducible gene expression in the murine immune response. We extracted primary CD4 splenocytes from inbred strains A/J, C57BL/6J, BALB/c, DBA/2J, and 129x1/SvJ (3 animals/strain) and measured mRNA transcript levels using microarrays in both basal state and four hours after stimulation with PMA/Ionomycin. We report strain-specific genome-wide differences in mRNA expression between A/J, Balb/c, C57BL/6J, DBA/2J and 129X1/SvJ inbred mice in CD4 splenocytes in basal, stimulated (4hr, PMA/I) states.

ORGANISM(S): Mus musculus

PROVIDER: GSE36551 | GEO | 2019/09/23

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Imiquimod (IMQ) produces a cutaneous phenotype in mice frequently studied as an acute model of human psoriasis. Whether this phenotype depends on strain or sex has never been systematically investigated on a large scale. Such effects, however, could lead to conflicts among studies, while further impacting study outcomes and efforts to translate research findings. Methods: RNA-seq was used to evaluate the psoriasiform phenotype elicited by IMQ in both sexes of 7 mouse strains (C57BL/6J, BALB/cJ, CD1, DBA/1J, FVB/NJ, 129X1/SvJ and MOLF/EiJ). Results: In most strains, IMQ altered gene expression in a manner consistent with human psoriasis, partly due to innate immune activation and decreased homeostatic gene expression. The IMQ response of MOLF males was aberrant, however, with decreased expression of differentiation-associated genes (elevated in other strains). Key aspects of the IMQ response differed between the two most commonly studied strains (BALB/c and C57BL/6). Compared with BALB/c, the C57BL/6 phenotype showed increased expression of genes associated with DNA replication, IL-17A activation and CD8+ T cells, but decreased expression of genes associated with interferon signaling and CD4+ T cells. Surprisingly, although IMQ-induced expression shifts mirrored psoriasis, correspondence was similar or better for other human skin diseases (e.g., eschars, acne, atopic dermatitis). For BALB/c, MOLF, and 129X1 strains, genes altered by IMQ corresponded better to those altered in human skin infections or wounds compared with those altered in psoriasis lesions. Conclusions: These findings demonstrate strain-dependent aspects of IMQ dermatitis that warrant consideration in planning and interpreting experimental studies. We have further shown that IMQ does not uniquely model psoriasis but in fact triggers a core set of pathways active in diverse skin diseases. These observations challenge the view of IMQ dermatitis as a mouse phenotype uniquely appropriate for studying psoriasis as opposed to other human skin conditions.

Dataset Information

Influence of genetic variation on inducible gene expression in murine CD4+ splenocytes.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets