Iron metabolism in TS65DN mice, a model of down syndrome
Ended Project Grant Awarded Last action
- Award ID
- R15AG077421
- Recipient
-
University Of Health Sciences And Pharmacy In ST. Louis UEI NMMKG6CCEMW4
- Awarding agency
-
National Institute on Aging
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,395,990
Award facts
- Assistance listing
- 93.310 Trans-NIH Research Support
- Completion date
- Originally
- Funding agency
- Office of the Director National Institutes of Health, Department of Health and Human Services
- Place of performance
- St. Louis, MO 63110, USA
Award details come from USAspending.gov.
Description
- Abstract
- Down syndrome (DS) is a developmental disability that typically results from the triplication of chromosome 21 with an occurrence of 1 in 700 live births. Chromosome 21 triplication may alter normal gene expression and lead to intellectual disability, early onset alzheimer's disease, congenital heart disease, hematologic disorders, among other conditions. Dysregulation of iron homeostatic mechanisms may be an underlying factor in clinical outcomes associated with DS. Iron is a trace element well-known for its involvement with physiological processes that include oxygen transport, inflammatory response, energy metabolism, and DNA synthesis. Iron homeostatic dysregulation in DS could lead to compromised plasma iron levels and tissue iron accumulation that catalyzes the production of reactive oxygen radical species (ROS). Despite reports of iron status parameters in DS there is a lack of clear and comprehensive understanding of iron homeostatic regulation among this population of individuals. The TS65DN mouse is an established model of DS that may hold considerable value to study mechanistic factors that regulate iron homeostasis in DS. The objective of this project is to delineate SEX and age-related alterations in iron homeostatic regulation over the adult lifespan of TS65DN mice and to associate changes in iron regulation with tissue iron levels and oxidative stress. In these studies, tissues (brain, liver, and plasma) from TS65DN mice and wild-type (WT) colony controls at 3, 12, and 18 months of age will be studied to address two integrated specific aims: 1) depict the iron homeostatic phenotype of TS65DN mice across the adult lifespan, and 2) determine the impact of hypoxia exposure (10% inspired O2) on systemic and tissue iron homeostasis, hematologic profile, and tissue oxidative stress in TS65DN mice. The first aim of this proposal will establish the utility of the TS65DN mouse model to study iron status and iron homeostatic regulation in DS. IT is hypothesized that TS65DN mice will show greater inflammation that will promote an iron regulation response leading to lower plasma compartment iron and elevated iron in the storage compartment. Elevated tissue iron in TS65DN mice is postulated to associate with greater oxidative injury. The second aim will employ hypoxia exposure to alter iron homeostatic regulation of TS65DN and WT mice to test the hypothesis that hypoxia induced iron distribution shifts from storage to the plasma compartment will reduce TS65DN tissue iron toxicity and improve the hematologic profile. Furthermore, IT is hypothesized that male mice will display greater iron status and oxidative stress than females, with TS65DN showing greater levels than WT controls. As iron metabolism dysregulation and tissue iron accumulation can become more prominent with aging, understanding iron metabolism in DS is of utmost importance as life expectancy of this population has dramatically improved over the past several decades.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $465,330 | |
| Amendment | $465,330 | |
| Original award | $465,330 |
Quick answers
Who received award R15AG077421?
R15AG077421 was awarded to University Of Health Sciences And Pharmacy In ST. Louis by National Institute on Aging (National Institutes of Health) on September 1, 2022.
How much is award R15AG077421 worth?
$1,395,990 has been obligated on R15AG077421.
Which agency awarded R15AG077421?
National Institute on Aging (National Institutes of Health) awarded R15AG077421, with funding from Office of the Director (National Institutes of Health).
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award