26. Prediction of imminent death in mice used for longevity research

Ray, Maria A; Johnston, Nancy; Verhulst, Steve; Toth, Linda A

doi:10.1016/j.exger.2008.08.040

Cited by 48 publications

(73 citation statements)

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“…8; P Ͻ 0.001). Furthermore, the mice infected with the WT and anr-complemented strains had lower external body temperatures, a marker of imminent death (54), than mice infected with the ⌬anr mutant strain. Mice infected with the ⌬anr mutant strain had a body temperature near the baseline (27.9 Ϯ 0.9°C), while mice infected with the WT had a significantly lower body temperature (22.8 Ϯ 0.4°C) at 24 h. The differences between the two groups in body temperatures and the number of CFU recovered suggest that Anr plays a role in this acute-phase infection model.…”

Section: Resultsmentioning

confidence: 99%

Anr and Its Activation by PlcH Activity in Pseudomonas aeruginosa Host Colonization and Virulence

et al. 2013

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bPseudomonas aeruginosa hemolytic phospholipase C (PlcH) degrades phosphatidylcholine (PC), an abundant lipid in cell membranes and lung surfactant. A ⌬plcHR mutant, known to be defective in virulence in animal models, was less able to colonize epithelial cell monolayers and was defective in biofilm formation on plastic when grown in lung surfactant. Microarray analyses found that strains defective in PlcH production had lower levels of Anr-regulated transcripts than the wild type. PC degradation stimulated the Anr regulon in an Anr-dependent manner under conditions where Anr activity was submaximal because of the presence of oxygen. Two PC catabolites, choline and glycine betaine (GB), were sufficient to stimulate Anr activity, and their catabolism was required for Anr activation. The addition of choline or GB to glucose-containing medium did not alter Anr protein levels, growth rates, or respiratory activity, and Anr activation could not be attributed to the osmoprotectant functions of GB. The ⌬anr mutant was defective in virulence in a mouse pneumonia model. Several lines of evidence indicate that Anr is important for the colonization of biotic and abiotic surfaces in both P. aeruginosa PAO1 and PA14 and that increases in Anr activity resulted in enhanced biofilm formation. Our data suggest that PlcH activity promotes Anr activity in oxic environments and that Anr activity contributes to virulence, even in the acute infection phase, where low oxygen tensions are not expected. This finding highlights the relationships among in vivo bacterial metabolism, the activity of the oxygen-sensitive regulator Anr, and virulence.

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Section: Resultsmentioning

confidence: 99%

Anr and Its Activation by PlcH Activity in Pseudomonas aeruginosa Host Colonization and Virulence

et al. 2013

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“…The veterinarian and researchers examined the mice for severity of illness or impairment, and animals were euthanized if they were not likely to survive for another 48 h. The likelihood of survival was based on the occurrence of at least two of the following clinical signs set forth by The Jackson Laboratory (Yuan et al 2009). The signs included failure to drink or eat, extreme weight loss over a short period of time, severe weakness based on responsiveness to touch, serious locomotor impairments, or tumors that had ulcerated or were bleeding (Ray et al 2010). The date of death for each mouse was logged, and the number of days lived was calculated and used for analysis.…”

Section: Longevitymentioning

confidence: 99%

Long-term α1B-adrenergic receptor activation shortens lifespan, while α1A-adrenergic receptor stimulation prolongs lifespan in association with decreased cancer incidence

Collette

Amoth

et al. 2014

AGE

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The α 1 -adrenergic receptor (α 1 AR) subtypes, α 1A AR and α 1B AR, have differential effects in the heart and central nervous system. Long-term stimulation of the α 1A AR subtype prolongs lifespan and provides cardio-and neuro-protective effects. We examined the lifespan of constitutively active mutant (CAM)-α 1B AR mice and the incidence of cancer in mice expressing the CAM form of either the α 1A AR (CAM-α 1A AR mice) or α 1B AR. CAM-α 1B AR mice have a significantly shortened lifespan when compared with wild-type (WT) animals; however, the effect was sex dependent. Female CAM-α 1B AR mice lived significantly shorter lives, while the median lifespan of male CAM-α 1B AR mice was not different when compared with that of WT animals. There was no difference in the incidence of cancer in either sex of CAM-α 1B AR mice. The incidence of cancer was significantly decreased in CAM-α 1A AR mice when compared with that in WT, and no sex-dependent effects were observed. Further study is warranted on cancer incidence after activation of each α 1 AR subtype and the effect of sex on lifespan following activation of the α 1B AR. The implications of a decrease in cancer incidence following long-term α 1A AR stimulation could lead to improved treatments for cancer.

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“…More objective or quantitative criteria include (1) failure to eat and drink (determined by food hopper and water bottle weights), (2) loss of body weight, 69,131 and (3) body temperature (as determined by telemetry). 183 Telemetry transponders offer advantages of rapid definitive animal identification and temperature measurements, but transponders, microchips, or other implanted devices may contribute to neoplasia and mortality in susceptible mice. 30,68,134,180,223…”

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confidence: 99%

Pathobiology of Aging Mice and GEM

2012

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The use of induced and spontaneous mutant mice and genetically engineered mice (and combinations thereof) to study cancers and other aging phenotypes to advance improved functional human life spans will involve studies of aging mice. Genetic background contributes to pathology phenotypes and to causes of death as well as to longevity. Increased recognition of expected phenotypes, experimental variables that influence phenotypes and research outcomes, and experimental design options and rationales can maximize the utility of genetically engineered mice (GEM) models to translational research on aging. This review aims to provide resources to enhance the design and practice of chronic and longevity studies involving GEM. C57BL6, 129, and FVB/N strains are emphasized because of their widespread use in the generation of knockout, transgenic, and conditional mutant GEM. Resources are included also for pathology of other inbred strain families, including A, AKR, BALB/c, C3H, C57L, C58, CBA, DBA, GR, NOD.scid, SAMP, and SJL/J, and non-inbred mice, including 4WC, AB6F1, Ames dwarf, B6, 129, B6C3F1, BALB/c,129, Het3, nude, SENCAR, and several Swiss stocks. Experimental strategies for long-term cross-sectional and longitudinal studies to assess causes of or contributors to death, disease burden, spectrum of pathology phenotypes, longevity, and functional healthy life spans (health spans) are compared and discussed.

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26. Prediction of imminent death in mice used for longevity research

Cited by 48 publications

References 0 publications

Anr and Its Activation by PlcH Activity in Pseudomonas aeruginosa Host Colonization and Virulence

Anr and Its Activation by PlcH Activity in Pseudomonas aeruginosa Host Colonization and Virulence

Long-term α1B-adrenergic receptor activation shortens lifespan, while α1A-adrenergic receptor stimulation prolongs lifespan in association with decreased cancer incidence

Pathobiology of Aging Mice and GEM

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