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Comparative analysis of genome-wide gene expression profiles in heart, liver, spleen, ears and bone marrow in the murine strains of MRL/MpJ, C57B/6J, and Balb/C

ABSTRACT: The MRL/MpJ mouse strain is known as a model of mammalian regeneration. The strain exhibits an unusual capacity in regenerative wound healing manifested by scarless ear-hole closure and enhanced regeneration response reported in other organs. A significant feature of the strain is that the adult MRL/MpJ mouse retains several embryonic biochemical characteristics, including increased expression of stem cell markers. As the regenerative response after injury is rather limited in mammals the MRL/MpJ mouse is a great model to study the molecular and cellular basis of scarless wound healing. We report here the analysis of genome-wide transcriptomic profiles in the heart, ear, spleen, liver and bone marrow of the MRL/MpJ mouse. We used gene expression microarray, which interrogates 44.170 of mouse transcripts, in order to identify the genes exhibiting remarkable differences in expression in the MRL/MpJ mouse compared to two reference strains: C57BL/6J and BALB/c. The comparison revealed hundreds of differentially expressed transcripts. Significant enrichments of genes engaged in retinol metabolism, peroxisome proliferator-activated receptor (PPAR), wound healing, and homeobox pathways distinguishes the differentially expressed transcripts up-regulated in the MRL/MpJ mouse, whereas the genes related to immune response, including including response to wounding are greatly enriched among those down-regulated. The same functional categories were associated with remarkable parallels between the transcriptomic patterns in murine neonates and the adult MRL/MpJ mouse.

ORGANISM(S): Mus musculus

PROVIDER: GSE64624 | GEO | 2015/12/30

SECONDARY ACCESSION(S): PRJNA271474

REPOSITORIES: GEO

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Project description:Cryptorchidism and scrotal heating result in abnormal spermatogenesis but the mechanism(s) proscribing this temperature sensitivity are unknown. It was previously reported that the AKR/N or MRL/MpJ-+/+ mouse testis is more heat resistant than the testis from the C57BL/6 strain. We have attempted to probe into the mechanism(s) involved in heat sensitivity by examining global gene expression profiles of normal and heat-treated testes from C57BL/6, AKR/N and MRL/MpJ-+/+ mice by microarray analysis. In the normal C57BL/6 testis, 415 and 416 transcripts were differentially expressed (at least two-fold higher or lower) when compared to the normal AKR/N and MRL/MpJ-+/+ testis, respectively. The AKR/N and MRL/MpJ-+/+ strains revealed 268 differentially expressed transcripts between them. There were 231 transcripts differentially expressed between C57BL/6 and two purported heat-resistant strains, AKR/N and MRL/MpJ-+/+. Next, the testes of C57BL/6 and AKR/N mice were exposed to 43ºC for 15 min and harvested at different time points for TUNEL studies and microarrays. An increase of TUNEL-positive germ cell numbers was significant 8 hr after heat exposure in the C57BL/6 mouse. However, this increase was not observed in the AKR/N mouse until 10 hr after heat exposure. All tubules showed germ cell loss and disruption in C57BL/6 testis 24 hr after heat shock. In contrast, although a number of seminiferous tubules showed an abnormal morphology 24 hr post-heat shock in the AKR/N mouse, many tubules still retained a normal structure. Numerous transcripts exhibited differential regulation between the two strains within 24 hours after heat exposure. The differentially expressed transcripts in the testes 8 hr after heat exposure were targeted to identify the genes involved in the initial response rather than those due to germ cell loss. Twenty transcripts were significantly down-regulated and 19 genes were up-regulated by hyperthermia in C57BL/6 and did not show a parallel change in the AKR/N testis. Conversely, heat shock resulted in 30 up-regulated transcripts and 31 down-regulated transcripts in AKR/N that were not similarly regulated in C57BL/6. A number of genes shared similar differential expression patterns and differential regulation by hyperthermia in both strains of mice. Taken together, the present study indicates the diverse genetic backgrounds in the three strains lead to major differences in normal testis gene expression profiles while the differences in heat shock responses involves a significantly smaller number of genes. The data generated may provide insights regarding gene networks and pathways involved in heat stress and their relationship to spermatogenesis.

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Comparative analysis of genome-wide gene expression profiles in heart, liver, spleen, ears and bone marrow in the murine strains of MRL/MpJ, C57B/6J, and Balb/C

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