Project description:We performed RNAseq on mouse progranulin deficient and humanized mouse progranulin deficient cortical tissue at 18 months to investigate the functional differences between mouse and human progranulin and identify transcriptomic changes for therapeutic endpoints.
Project description:aCGH analysis of murine transgenic liver tissues affected with HCC, hybridized with age (18 months) and sex matched C57BL/6 mice. Moreover, 18months old C57BL/6 livers were hybridized with independent 18 months old C57BL/6 livers for control. Keywords: Array comparative genomic hybridization analysis (aCGH).
Project description:Breast cancer is an age-related cancer in women with two peaks, one at 50 and one at 70 years of age. Here we used two conditional genetically engineered mouse models of breast cancer risk to study mammary gland transcriptional changes that occur as female mice age from 12 to 30 months of age, paralleling aging from 58 to 85 years of age in women. The two models express either mammary epithelial cell-targeted Estrogen Receptor (ER) alpha (Esr1) or Aromatase (CYP19A1A) over-expression beginning at age 12 or 18 months of age. Both of these risk factors increase estrogen pathway signaling, either directly though the receptor or by increasing local estrogen production. The goals of the study are to determine how quickly significant transcriptional changes occur in the mammary gland following transgene induction, to determine how the transcriptome becomes modified as the mice age past reproductive senescence through old and very old life stages, and to identify similarities and differences in the transcriptomes between the two risk conditions at different ages and conditions. The first specific objective of this transcriptome-based study is to identify significantly differentially expressed genes within each model between different ages and times of transgene induction. This includes transcriptional changes induced by 1 week, 6, 12 and 18 months of transgene expression with transgene expression initiated at age 12 months as well as transcriptional changes induced by 1 week and 6 months of transgene expression initiated at age 18 months. The second specific objective is to compare the two models at different ages (12, 18, 24 and 30 months of age) and different transgene induction times (6, 12 and 18 months) to identify differentially expressed genes between the models. Comparative control mice from each model include age 18- and 24-month-old mice without transgene induction.
Project description:aCGH analysis of murine transgenic liver tissues affected with HCC, hybridized with age (18 months) and sex matched C57BL/6 mice. Moreover, 18months old C57BL/6 livers were hybridized with independent 18 months old C57BL/6 livers for control. Keywords: Array comparative genomic hybridization analysis (aCGH). Independent HCC of AlbLTab mice were hybridized with independent C57BL/6 mice.
Project description:Age-related decline in brain endothelial cell (BEC) function critically contributes to cerebrovascular and neurodegenerative disease. Comprehensive atlases of the BEC transcriptome have become available but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting (MACS)-based mouse BEC enrichment protocol compatible with high-resolution mass-spectrometry based proteomics. In this experiment, first we have compared MACS sorted BECs across multiple time points between 3 and 18 months of age. Using unsupervised cluster analysis, we found a segregation of age-related protein dynamics with biological functions including a downregulation of vesicle-mediated transport. Our approach uncovered changes not picked up by transcriptomic studies such as accumulation of vesicle cargo and receptor ligands including Apoe. Therefor in our next proteomics experiment we compared BECs from 3-months-old Apoe-KO and WT mice and found 111 and 103 proteins to be up- and downregulated, respectively. Comparing the BEC proteomic signature of young Apoe-KO mice with the signature of aged (18-months-old) WT mice we found a positive correlation suggesting an accelerating effect of Apoe deficiency on BEC aging.
Project description:Background: The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis. Methods: To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol. Results: Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in thepresence of SCAs was seen in tumours of patients between 12 and 18 months and over 18 months of age at diagnosis, respectively (P<0.04). A significant correlation (P<0.03) was observed between number of SCAs per tumour and age. Event-free (EFS) andoverall survival (OS) were calculated in both age groups, according to both the presence and number of SCAs. In older patients, a poorer survival was associated with the presence of SCAs (EFS<46% vs 75%, P<0.023; OS<66.8% vs 100%, P<0.003). Moreover, OS of older patients inversely correlated with number of SCAs (P<0.002). Finally, SCAs provided additional prognostic information beyond histoprognosis, as their presence was associated with poorer OS in patients over 18 months with unfavourable International Neuroblastoma Pathology Classification (INPC) histopathology (P<0.018). Conclusions: The presence of SCAs is a negative prognostic marker that impairs outcome of patients over the age of 18 months with localised unresectable NB without MYCN amplification, especially when more than one SCA is present. Moreover, in older patients with unfavourable INPC tumour histoprognosis, the presence of SCAs significantly affects OS.
