Selected Grantee Publications
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- 4 results found
- nhlbi
- Alzheimer's Disease
- Women's Health
Establishing the Hybrid Rat Diversity Program: A Resource for Dissecting Complex Traits
Dwinell et al., Mammalian Genome. 2025.
https://pubmed.ncbi.nlm.nih.gov/39907792
Rat models have been extensively used for studying human complex disease mechanisms, behavioral phenotypes, and environmental factors and for discovering and developing drugs. Systems genetics approaches have been used to study the effects of both genetic variation and environmental factors. This approach recognizes the complexity of common disorders and uses intermediate phenotypes to find relationships between genetic variation and clinical traits. This article describes the Hybrid Rat Diversity Program (HDRP) at the Medical College of Wisconsin, which involves 96 inbred rat strains and aims to provide a renewable and reusable resource in terms of the HRDP panel of inbred rat strains, the genomic data derived from the HRDP strains, and banked resources available for additional studies. Supported by ORIP (R24OD024617) and NHLBI.
Impaired Skeletal Development by Disruption of Presenilin-1 in Pigs and Generation of Novel Pig Models for Alzheimer's Disease
Uh et al., Journal of Alzheimer's Disease. 2024.
https://pubmed.ncbi.nlm.nih.gov/39177593/
This study explored the effects of presenilin 1 (PSEN1) disruption on vertebral malformations in male and female PSEN1 mutant pigs. Researchers observed significant skeletal impairments and early deaths in pigs with a PSEN1 null mutation, mirroring phenotypes seen in mouse models of Alzheimer’s disease (AD). This porcine model provides valuable insights into pathological hallmarks of PSEN1 mutations in AD, offering a robust platform of therapeutic exploration. The findings establish pigs as an essential translational model for AD, enabling advanced studies on pathophysiology and treatment development for human skeletal and neurological conditions. Supported by ORIP (U42OD011140), NHLBI, NIA, NIAID.
X Chromosome Agents of Sexual Differentiation
Arnold et al., Nature Reviews Endocrinology. 2022.
https://www.doi.org/10.1038/s41574-022-00697-0
Many diseases affect one sex disproportionately. A major goal of biomedical research is to understand which sex-biasing factors influence disease severity and to develop therapeutic strategies to target these factors. Two groups of such agents are sex chromosome genes and gonadal hormones. Researchers use the “four core genotypes” model to enable comparisons among animals with different sex chromosomes but the same type of sex hormones, which allows investigators to distinguish disease mechanisms influenced by the sex chromosomes. Supported by ORIP (R01OD030496, R21OD026560), NICHD, NIDDK, and NHLBI.
Common and Divergent Features of T Cells From Blood, Gut, and Genital Tract of Antiretroviral Therapy–Treated HIV+ Women
Xie et al., Journal of Immunology. 2022.
https://www.doi.org/10.4049/jimmunol.2101102
T cells residing in mucosal tissues play important roles in homeostasis and defense against microbial pathogens, but how organ system environments affect the properties of resident T cells is relatively unknown. Researchers phenotyped T cells in the gut and reproductive tract using blood and tissue samples from women with HIV who have achieved viral suppression via antiretroviral therapy. The T cells exhibited differing expression of CD69 and CD103 markers, whereas resident memory CD8+ T cells from the female reproductive tract expressed PD1 preferentially. Additionally, CXCR4+ T inflammatory mucosal cells expressed multiple chemokine receptors differentially. These results suggest that T cells take on distinct properties in different mucosal sites, which allows them to tailor activities to their surrounding milieu. This study offers important insights for reproductive medicine in women. Supported by ORIP (S10OD018040), NHLBI, NIAID, and NIDDK.