A systematic review of the development and application of home cage monitoring in laboratory mice and rats

Abstract

Background: Traditionally, in biomedical animal research, laboratory rodents are individually examined in test apparatuses outside of their home cages at selected time points. However, the outcome of such tests can be influenced by various factors and valuable information may be missed when the animals are only monitored for short periods. These issues can be overcome by longitudinally monitoring mice and rats in their home cages. To shed light on the development of home cage monitoring (HCM) and the current state-of-the-art, a systematic review was carried out on 521 publications retrieved through PubMed and Web of Science.

Results: Both the absolute (~ × 26) and relative (~ × 7) number of HCM-related publications increased from 1974 to 2020. There was a clear bias towards males and individually housed animals, but during the past decade (2011-2020), an increasing number of studies used both sexes and group housing. In most studies, animals were kept for short (up to 4 weeks) time periods in the HCM systems; intermediate time periods (4-12 weeks) increased in frequency in the years between 2011 and 2020. Before the 2000s, HCM techniques were predominantly applied for less than 12 h, while 24-h measurements have been more frequent since the 2000s. The systematic review demonstrated that manual monitoring is decreasing in relation to automatic techniques but still relevant. Until (and including) the 1990s, most techniques were applied manually but have been progressively replaced by automation since the 2000s. Independent of the year of publication, the main behavioral parameters measured were locomotor activity, feeding, and social behaviors; the main physiological parameters were heart rate and electrocardiography. External appearance-related parameters were rarely examined in the home cages. Due to technological progress and application of artificial intelligence, more refined and detailed behavioral parameters have been investigated in the home cage more recently.

Conclusions: Over the period covered in this study, techniques for HCM of mice and rats have improved considerably. This development is ongoing and further progress as well as validation of HCM systems will extend the applications to allow for continuous, longitudinal, non-invasive monitoring of an increasing range of parameters in group-housed small rodents in their home cages.

Keywords: Animal welfare; Behavior; History; Home cage monitoring; Mice; Physiology; Rats; Refinement; Rodents; Sex bias.

Fig. 1

PRISMA flow diagram

Fig. 2

Historical change in the publication rate. A Absolute number of included publications on home cage monitoring (HCM) of mice and rats (n = 520 publications). B The ratio of HCM references (n = 520 publications) relative to the overall number of studies in mice or rats (n = 3,124,961 publications) published in the years 1974 to 2020. The overall number of studies in mice or rats was retrieved through a search in PubMed using the search string: “mice”[MeSH Terms] OR “mice”[All Fields] OR “rats”[MeSH Terms] OR “rats”[All Fields]; filter: other animals)

Fig. 3

Historical change in the number of publications using male and/or female mice (A), publications investigating specific disease models (B), and publications employing single or group housing (C) (n = 520 publications)

Fig. 4

Mouse and rat strains that were used in the included publications in the years 1974 to 2021 (data obtained from n = 521 publications). More than one strain could be used in a study. Strains that were indicated twice or once only, were summarized under “other”

Fig. 5

Historical change in the number of custom-built and commercially available home cage monitoring (HCM) systems. More than one system could be applied in a study. In n = 126 cases custom-built HCM systems and in n = 219 cases commercially available HCM systems were used (multiple HCM systems were applied in n = 28 studies). Studies in which no HCM system was used were excluded from this figure

Fig. 6

Historical change in the duration of housing and monitoring in the home cage: A duration spent in the home cage (n = 520 publications), B overall duration of measurement (n = 667 techniques), C duration of measurement per day (n = 699 techniques) using a home cage monitoring technique. For B and C, it must be noted that more than one technique for data measurement could be used in a study. If one of the techniques used to investigate parameters of interests could not be extracted from the publication, this technique was excluded for B and C. Note the differences in the scaling of the y-axis

Fig. 7

Historical change in home cage monitoring techniques for laboratory mice and rats (data obtained from n = 520 publications). More than one technique could be indicated in a publication. If one of the techniques used to investigate parameters of interests could not be extracted from the publication but information on the degree of automatization was given, this technique was excluded for A and included for B. A Number of techniques used in the included publications in the defined time periods. Other: infrared thermometer (n = 1), automatic food dispenser (n = 1), impedance pneumography (n = 1), flowmeter circuit (n = 1), lever (n = 2), brain imaging cameras (n = 2), fiber photometry system (n = 1), cardiotachometer (n = 1), thermal imaging (n = 1). B Number of manual and automated techniques that were applied in the publications included

Fig. 8

Historical change in monitoring of A behavioral parameters, B physiological parameters, and C external appearance-related parameters in mice and rats in their home cages (data obtained from n = 520 publications). More than one application (i.e., parameter) could be indicated in a publication. If the same parameter was investigated using different techniques in a study, the parameter was counted only once for this study. Examples for abnormal behaviors were infanticide, barbering, and stereotypy. Other behaviors (each n = 1): sneezing, sign of pain or distress (not further specified), clinical signs (not further specified), curiosity/alertness, champing behavior, twitches, and behavior not further specified. Note the differences in the scaling of the y-axis