Male rat leukocyte population dynamics predict a window for intervention in aging.

Many age-associated changes in the human hematopoietic system have been reproduced in murine models; however, such changes have not been as robustly explored in rats despite the fact these larger rodents are more physiologically similar to humans. We examined peripheral blood of male F344 rats ranging from 3 to 27 months of age and found significant age-associated changes with distinct leukocyte population shifts. We report CD25 CD4 population frequency is a strong predictor of healthy aging, generate a model using blood parameters, and find rats with blood profiles that diverge from chronologic age indicate debility; thus, assessments of blood composition may be useful for non-lethal disease profiling or as a surrogate measure for efficacy of aging interventions.

Impact of Large Granular Lymphocyte Leukemia on Blood DNA Methylation and Epigenetic Clock Modeling in Fischer 344 Rats.

Age-dependent differences in methylation at specific cytosine-guanine (CpG) sites have been used in "epigenetic clock" formulas to predict age. Deviations of epigenetic age from chronological age are informative of health status and are associated with adverse health outcomes, including mortality. In most cases, epigenetic clocks are performed on methylation from DNA extracted from circulating blood cells.

A rat epigenetic clock recapitulates phenotypic aging and co-localizes with heterochromatin.

Robust biomarkers of aging have been developed from DNA methylation in humans and more recently, in mice. This study aimed to generate a novel epigenetic clock in rats-a model with unique physical, physiological, and biochemical advantages-by incorporating behavioral data, unsupervised machine learning, and network analysis to identify epigenetic signals that not only track with age, but also relates to phenotypic aging. Reduced representation bisulfite sequencing (RRBS) data was used to train an epigenetic age (DNAmAge) measure in Fischer 344 CDF (F344) rats.

Commensal bacteria contribute to insulin resistance in aging by activating innate B1a cells.

Aging in humans is associated with increased hyperglycemia and insulin resistance (collectively termed IR) and dysregulation of the immune system. However, the causative factors underlying their association remain unknown. Here, using "healthy" aged mice and macaques, we found that IR was induced by activated innate 4-1BBL B1a cells.

Diversity of murine norovirus strains isolated from asymptomatic mice of different genetic backgrounds within a single U.S. research institute.

Antibody prevalence studies in laboratory mice indicate that murine norovirus (MNV) infections are common, but the natural history of these viruses has not been fully established. This study examined the extent of genetic diversity of murine noroviruses isolated from healthy laboratory mice housed in multiple animal facilities within a single, large research institute- the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIAID-NIH) in Bethesda, Maryland, U.S.

Detection of Spironucleus muris in unpreserved mouse tissue and fecal samples by using a PCR assay.

The purpose of this study was to develop a rapid DNA isolation method and a sensitive and specific PCR assay for detecting Spironucleus muris in mouse tissue and fecal samples. A PCR assay based on the carboxy terminus of the elongation factor 1a gene was developed; the PCR product was confirmed by nucleic acid sequencing and nested PCR. The new PCR assay then was used to test feces from animals that had been screened for S.

Suboptimal ability of dirty-bedding sentinels to detect Spironucleus muris in a colony of mice with genetic manipulations of the adaptive immune system.

Spironucleus muris is an unacceptable infectious agent for most rodent colonies. Exposure of sentinel mice to dirty bedding and examination of sentinel intestinal smears was not sufficient for identification of the extent of spironucleosis within 1 mouse room. Clinical abnormalities were not reported in the animals housed in the room despite extensive breeding and a preponderance of mice genetically engineered to have nonfunctional T and B cells.

Eradication of murine norovirus from a mouse barrier facility.

Murine norovirus (MNV) is a common viral infection of mice in many research facilities. MNV infects hematopoietic cells and alters their cellular morphology. Because of MNV's probable effects on the systemic immune response of infected mice the decision was made to eradicate the virus from 2 rooms containing infected animals in our vivarium.

Naturally occurring murine norovirus infection in a large research institution.

Murine norovirus (MNV) is a recently discovered infectious agent in mice and may be the most common naturally occurring infection of laboratory mice in North America. In 2005, we surveyed the Swiss Webster female sentinel mice in our institute's research facilities. Of the 4 facilities surveyed, 3 had sentinel mice that were positive for MNV antibodies, whereas our largest facility (which only receives mice directly from select vendors or by embryo rederivation directly into the facility) was apparently MNV-free.

Variation in organ volumes of matched BALB/c mice by microcomputed tomography analysis.

High-resolution microcomputed tomography technology has allowed researchers to use live mice to address questions that previously could be answered only at necropsy. Serial analyses of the same mouse allow tissue changes to be followed over time. The ability to follow a single mouse noninvasively can decrease the total number of mice required for the study.

A retrospective study of idiopathic ulcerative dermatitis in mice with a C57BL/6 background.

Idiopathic ulcerative dermatitis is a well-recognized disease in C57BL mice and related strains. This disease manifests as a pruritic dermatitis with resulting self-mutilation, dermal ulceration, necrosis, and fibrosis. Ulcerative dermatitis has the ability to confound ongoing research by causing systemic pathologic changes, such as lymphadenopathy and splenomegaly.

Detection and clearance of Syphacia obvelata infection in Swiss Webster and athymic nude mice.

Our routine health-surveillance program is based on use of the Swiss Webster mouse, with sentinels submitted for testing every 7 weeks. Athymic nude (nu/nu) mice are used as an adjunct method to detect pinworm infections. The premise for the use of the nude mouse was based on research that revealed the thymus as necessary to confer resistance to pinworm infections.