Automated monitoring of mouse feeding and body weight for continuous health assessment.

Routine health assessment of laboratory rodents can be improved using automated home cage monitoring. Continuous, non-stressful, objective assessment of rodents unaware that they are being watched, including during their active dark period, reveals behavioural and physiological changes otherwise invisible to human caretakers. We developed an automated feeder that tracks feed intake, body weight, and physical appearance of individual radio frequency identification-tagged mice in social home cages. Here, we experimentally induce illness via lipopolysaccharide challenge and show that this automated tracking apparatus reveals sickness behaviour (reduced food intake) as early as 2-4 hours after lipopolysaccharide injection, whereas human observers conducting routine health checks fail to detect a significant difference between sick mice and saline-injected controls. Continuous automated monitoring additionally reveals pronounced circadian rhythms in both feed intake and body weight. Automated home cage monitoring is a non-invasive, reliable mode of health surveillance allowing caretakers to more efficiently detect and respond to early signs of illness in laboratory rodent populations.

Energy reallocation to breeding performance through improved nest building in laboratory mice.

Mice are housed at temperatures (20-26 °C) that increase their basal metabolic rates and impose high energy demands to maintain core temperatures. Therefore, energy must be reallocated from other biological processes to increase heat production to offset heat loss. Supplying laboratory mice with nesting material may provide sufficient insulation to reduce heat loss and improve both feed conversion and breeding performance. Naïve C57BL/6, BALB/c, and CD-1 breeding pairs were provided with bedding alone, or bedding supplemented with either 8 g of Enviro-Dri, 8 g of Nestlets, for 6 months. Mice provided with either nesting material built more dome-like nests than controls. Nesting material improved feed efficiency per pup weaned as well as pup weaning weight. The breeding index (pups weaned/dam/week) was higher when either nesting material was provided. Thus, the sparing of energy for thermoregulation of mice given additional nesting material may have been responsible for the improved breeding and growth of offspring.

Impact of nesting material on mouse body temperature and physiology.

In laboratories, mice are housed at 20-24 °C, which is below their lower critical temperature (≈30 °C). Thus, mice are potentially cold stressed, which can alter metabolism, immune function, and reproduction. These physiological changes reflect impaired wellbeing, and affect scientific outcomes. We hypothesized that nesting material would allow mice to alleviate cold stress by controlling their thermal microenvironment, thus insulating them, reducing heat loss and thermogenic processes. Naïve C57BL/6, CD-1, and BALB/c mice (24 male and 24 female/strain in groups of 3) were housed in standard cages at 20 °C either with or without 8 g nesting material for 4 weeks. Core body temperature was followed using intraperitoneal radio telemetry. The thermal properties of the nests were assessed using a thermal imaging camera, and related to nest quality. Higher scoring nests were negatively correlated with the mean radiated temperature and were thus more insulating. No effects of nesting material on body temperature were found. CD-1 mice with nesting material had higher end body weights than controls. No effect was seen in the other two strains. Mice with the telemetry implant had larger spleens than controls, possibly indicating an immune response to the implant or low level infection from the surgery. BALB/c mice express less mRNA for the UCP1 protein than mice without nesting material. This indicates that BALB/c's with nesting material do not utilize their brown fat to create heat as readily as controls. Nests can alleviate thermal discomfort by decreasing the amount of radiated heat and reduce the need for non-shivering thermogenesis. However, different strains appear to use different behavioral (through different primary modes of behavioral thermoregulation) and physiological strategies (utilizing thermogenesis to different degrees) to maintain a constant body temperature under cool standard laboratory ambient temperatures.

Heat or insulation: behavioral titration of mouse preference for warmth or access to a nest.

In laboratories, mice are housed at 20-24°C, which is below their lower critical temperature (≈30°C). This increased thermal stress has the potential to alter scientific outcomes. Nesting material should allow for improved behavioral thermoregulation and thus alleviate this thermal stress. Nesting behavior should change with temperature and material, and the choice between nesting or thermotaxis (movement in response to temperature) should also depend on the balance of these factors, such that mice titrate nesting material against temperature. Naïve CD-1, BALB/c, and C57BL/6 mice (36 male and 36 female/strain in groups of 3) were housed in a set of 2 connected cages, each maintained at a different temperature using a water bath. One cage in each set was 20°C (Nesting cage; NC) while the other was one of 6 temperatures (Temperature cage; TC: 20, 23, 26, 29, 32, or 35°C). The NC contained one of 6 nesting provisions (0, 2, 4, 6, 8, or 10g), changed daily. Food intake and nest scores were measured in both cages. As the difference in temperature between paired cages increased, feed consumption in NC increased. Nesting provision altered differences in nest scores between the 2 paired temperatures. Nest scores in NC increased with increasing provision. In addition, temperature pairings altered the difference in nest scores with the smallest difference between locations at 26°C and 29°C. Mice transferred material from NC to TC but the likelihood of transfer decreased with increasing provision. Overall, mice of different strains and sexes prefer temperatures between 26-29°C and the shift from thermotaxis to nest building is seen between 6 and 10 g of material. Our results suggest that under normal laboratory temperatures, mice should be provided with no less than 6 grams of nesting material, but up to 10 grams may be needed to alleviate thermal distress under typical temperatures.

Attachment of Mycobacterium avium subspecies paratuberculosis to bovine intestinal organ cultures: method development and strain differences.

Mycobacterium avium spp. paratuberculosis (MAP) causes chronic granulomatous inflammation of the intestinal tract in many species of animals, but the mechanisms of disease are poorly understood. Attachment of bacteria to epithelial cells is a critical step in pathogenesis of many mucosal diseases. The goal of these studies was to develop an in vitro method to study attachment of MAP to bovine intestinal epithelial cells. Short-term, bovine intestinal organ cultures were used to show a significant difference in the ability of radiolabelled MAP strains to attach to intestinal epithelium. We found significant differences in the ability of different strains of MAP to attach, but there were no differences in attachment among different regions of the intestinal tract. Examination of acid fast stained tissue sections of organ cultures demonstrated that organisms were located adjacent to mucosal epithelium or within goblet cells. Coating of the organisms with fibronectin, which has been shown to be involved in attachment of many mycobacteria, including MAP, affected the attachment of the MAP strains in different ways, but did not affect the overall attachment of the organisms to different regions of the gastrointestinal tract. This organ culture method should also prove useful for defining the molecular mechanisms of attachment and interactions of MAP with intestinal epithelium.