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Transcriptome analysis of adipose tissues of A. actinomycetemcomitans- and C. pneumoniae-infected apoE-deficient mice

ABSTRACT: The 14-week experiment included three groups: 1) the Acute Cpn group, with one C. pneumoniae inoculation at the age of 9 wks; 2) the Chronic Cpn group, with three C. pneumoniae inoculations at the age of 9, 11, and 13 wks; and 3) the control group, with three SPG inoculations at the age of 9, 11, and 13 wks. The mice were sacrificed at the age of 14 wks. The 24-week experiment included four groups: 1) the recurrent A. actinomycetemcomitans infection group, with ten A. actinomycetemcomitans inoculations once a week from the age of 14 to 23 wks; 2) the chronic C. pneumoniae infection group, with three C. pneumoniae inoculations at the age of 9, 11, and 13 wks; 3) the combined chronic C. pneumoniae and recurrent A. actinomycetemcomitans infection group, with three C. pneumoniae inoculations at the age of 9, 11, and 13 wks, and ten A. actinomycetemcomitans inoculations once a week from the age of 14 to 23 wks; and 4) the control group, with three SPG inoculations at the age of 9, 11, and 13 wks, and ten 0.9% NaCl inoculations once a week from the age of 14 to 23 wks. The mice were sacrificed at the age of 24 wks.Epididymal and inguinal AT gene expression was analyzed using an Illumina Mouse WG-6 v2.0 platform.

ORGANISM(S): Mus musculus

PROVIDER: GSE50647 | GEO | 2013/10/28

SECONDARY ACCESSION(S): PRJNA218196

REPOSITORIES: GEO

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Project description:Children are considered more sensitive to radiation-induced cancer than adults, yet any differences in genomic alterations associated with age at exposure and their underlying mechanisms remain unclear. We analyzed the mutation of key tumor suppressor genes in T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old). T-cell lymphoma incidence did not show any statistical differences among three irradiated groups; however, the frequency of loss of heterozygosity on chromosomes 11 and 19 showed opposing correlations with age at exposure. Ikaros on chromosome 11 was mutated frequently in the young adultâ??irradiation group (63%; 5/8), frequently incurring multiple independent hits (including deletions and mutations) or suffering a single hit predicted to result in a dominant negative protein (such as those lacking exon 4, an isoform we have designated Ik11, which lacks two of the four zincâ??finger domains important for DNA binding). Pten on chromosome 19 was mutated more frequently in tumors from infant- (67%; 10/15) compared with young adult-irradiated mice (13%; 1/8, P = 0.041). Despite the presence of homozygous Pten mutations, DNA copy number was unchanged in the infant-irradiation group, suggesting duplication of the mutated allele by chromosome mis-segregation or mitotic recombination. Taken together, our findings demonstrate that while deletions on chromosome 11 affecting the Ikaros locus are a prominent feature of young adult irradiation-induced T-cell lymphoma, tumors arising after infant irradiation suffer a second hit in the Pten gene by chromosome mis-segregation or recombination. This is the first report showing age-at-exposure associated radiation-induced genomic alterations in two key tumor suppressor genes linked to T-cell lymphomagenesis. These data are important for considering the risks associated with childhood exposure to radiation. 38 T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting at different ages (Infant: 1 week old (15 tumors), Adolescent: 4 weeks old (13 tumors), Young adult: 8 weeks old (10 tumors)) were analyzed.

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Transcriptome analysis of adipose tissues of A. actinomycetemcomitans- and C. pneumoniae-infected apoE-deficient mice

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