Project description:Hearts were collected from Pcyt2+/- male and female mice at 8 months of age The microarray approach allows the investigation of gene expression changes of all genes in Pcyt2+/- male and female hearts.
Project description:Hearts were collected from Pcyt2+/- male and female mice at 8 months of age The microarray approach allows the investigation of gene expression changes of all genes in Pcyt2+/- male and female hearts.
Project description:Background The contribution of glucocorticoids to sexual dimorphism in the heart is essentially unknown. Therefore, we sought to determine the sexually dimorphic actions of glucocorticoid signaling in cardiac function and gene expression. To accomplish this goal, we conducted studies on mice lacking glucocorticoid receptors (GR) in cardiomyocytes (cardioGRKO mouse model). Methods and Results Deletion of cardiomyocyte GR leads to an increase in mortality because of the development of spontaneous cardiac pathology in both male and female mice; however, females are more resistant to GR signaling inactivation in the heart. Male cardioGRKO mice had a median survival age of 6 months. In contrast, females had a median survival age of 10 months. Transthoracic echocardiography data showed phenotypic differences between male and female cardioGRKO hearts. By 3 months of age, male cardioGRKO mice exhibited left ventricular systolic dysfunction. Conversely, no significant functional deficits were observed in female cardioGRKO mice at the same time point. Functional sensitivity of male hearts to the loss of cardiomyocyte GR was reversed following gonadectomy. RNA‐Seq analysis showed that deleting GR in the male hearts leads to a more profound dysregulation in the expression of genes implicated in heart rate regulation (calcium handling). In agreement with these gene expression data, cardiomyocytes isolated from male cardioGRKO hearts displayed altered intracellular calcium responses. In contrast, female GR‐deficient cardiomyocytes presented a response comparable with controls. Conclusions These data suggest that GR regulates calcium responses in a sex‐biased manner, leading to sexually distinct responses to stress in male and female mice hearts, which may contribute to sex differences in heart disease, including the development of ventricular arrhythmias that contribute to heart failure and sudden death.
Project description:In this study cDNA microarrays were used to identify genes with sex-biased expression in mouse whole hearts of two age classes (2 months and 8 months of age). Experiment Overall Design: A total of 24 male and female C57BL/6 mice were sacrificed at two and eight months of age, respectively (n=6 per group). Isolated total RNAs were pooled according to sex and age and hybridized on Agilent cDNA microarrays (age-matched, male vs. female or vice versa). Four technical replicates were carried out with exchanged dye-labelled RNA probes (dye-swap) on two of them.
Project description:To compare the effects of biological sex (female/male) and age (4 mo./20 mo.) on C57BL/6J mouse hearts, we performed mRNA sequencing.
Project description:Model with functions depending on Age, Male, BP (Blood Pressure).
There are 3 disease states: Healthy, Sick, and Dead, where the Dead state is terminal. The yearly transition probabilities are: Healthy to Dead: Age/1000; Healthy to Sick: According to function F1 depending on Age and Male and BP; Sick to Healthy: 0.1; Sick to Dead: according to function F2 depending on Age and Male.
Pre-Transition Rules: Age increased by 1 and BP by Age/10 each simulation cycle. Post-Transition Rules: Treatment = BP>140 , becomes 1 when BP crosses 140 threshold; BP =BP-Treatment*10 , meaning a drop of 10 once treatment is applied; CostThisYear = Age + \Treatment*10 , cost depends on age and if treatment was taken; Cost= Cost + CostThisYear , it accumulates cost over time.
Initial conditions: Healthy = (50 Male, 50 Female with Age =1,2,...,50 for each individual), BP =120, Sick = (0,0) and Dead = (0,0).
Output: Number of men and women in each disease state for years 1-10 and their ages and costs in each state. A stratified report by male and female and young – up to age 30 and old above age 30 is produced.
Project description:We used LC-MS/MS based proteomics to identify changes in protein expression in the the female and male mouse hippocampus at 1, 2, and 4 months of age. This proteomics dataset was correlated with an accompanying mRNA dataset to identify genes that show mRNA changes in a different direction that their respective proteins. A modest correlation was found between mRNA and protein abundance in the mouse hippocampus (spearman rank coefficient = 0.53).
Project description:C57Bl6/J male and female mice were gonadectomized or not at the age of 12 months and then euthanized 12 months later at the age of 24 months. Half of the females received for 28 days an angiotensin II (AngII; 1.5 mg/kg/day) continuous infusion starting at the age of 23 months. The mice were provided with a running wheel during the 12 months after gonadectomy with the exception of the last month before euthanasia.
Project description:In a series of slice electrophysiology experiments, we demonstrated that female APPSwe-Psen1dE9 Alzheimer's disease model mice show greater impairments in hippocampal synaptic plasticity than male mice of the same age and genotype. Female APP/PS1 mice also showed greater impairments in behavioural associative memory, higher amyloid plaque burden and increased microglial activation in the hippocampus than males at age 4-5 months. We thus profiled hippocampal mRNA from these mice to investigate the underlying molecular mechanisms. Compared to wild-type mice of the same sex, we found that female APP/PS1 mice showed a greater upregulation of microglial and inflammatory genes than males. Moreover, downregulation of genes associated with memory and plasticity was observed uniquely in female APP/PS1 mice. These data provide insight into the potential mechanisms of the greater prevalence and faster progression of AD in females.
