meeting REVIEW Report of the 2007 RSPCA/UFAW Rodent Welfare Group meeting

PENNY HAWKINS (Se c r e ta r y ),1 ALLAN ies involving telemetry and champion- implantation of the E-pellet, the mice THORNHILL,2 GEORGE GRANT,3 ing in toxicology. Other became dehydrated and displayed blad- PAULINE BURGUN,4 PAUL ASHLEY,5 speakers addressed the evaluation of nest- der distension and skin discolouration. CLARE MILLUM,6 ROBERT HUBRECHT,7 ing material for mice with neurological Affected animals appeared to drag their KEVIN CURTIS8 an d MAGGY JEN- disorders, training in phenotyping and hindquarters on the substrate and sore NINGS1 good practice for sourcing rodents from areas were visible around the urethra and third countries. tail base. The welfare of our mice is very 1 Research Animals Department, important to us and any animals believed RSPCA, Wilberforce Way, The welfare implications of high dose to be suffering or developing complica- Southwater, West Sussex, RH13 9RS oestrogen pellets causing urinary calculi tions such as hard masses in the abdomen 2 Institute of Cancer Research, 15 in athymic nude mice were humanely killed. Cotswold Road, Sutton, Surrey, SM2 5NG Allan Thornhill, Institute of Cancer Autopsies revealed urinary calculi, or stru- 3 Gut Immunology Group, Rowett Research, 15 Cotswold Road, Sutton, Surrey, vite, composed of magnesium ammonium Research Institute, Greenburn Road, SM2 5NG phosphate, which is also found in human Bucksburn, Aberdeen, AB21 9SB bladder and kidney stones. It is mainly 4 Dept of Pharmacology, University Breast cancer models that use slow release caused by infection with urease-producing of Cambridge, Tennis Court Road, oestrogen (E) pellets in mice are widely bacteria such as Proteus spp. and is associ- Cambridge, CB1 1QJ used in many key laboratories and are cur- ated with abdominal surgery in the clinic. 5 Remo Technologies Ltd, Building rently important in breast cancer research, Microbial assessment showed that Proteus 227, Porton Down Science Park, but we have discovered some inherent type bacteria were indeed present in affect- Salisbury, Wiltshire, SP4 0JQ health and welfare problems for the ani- ed animals, but only in those implanted 6 Cancer Research UK, PO Box 123, mals. Fortunately, it has been possible to with an E-pellet, irrespective of whether Lincoln’s Inn Fields, London, reduce the impact of these adverse effects they had had surgery. We concluded that WC2A 3PX by modifying experimental protocols the E-pellet stimulated the normally com- 7 UFAW, The Old School, Brewhouse and ensuring that the mice are effectively mensal Proteus to proliferate and cause Hill, Wheathampstead, monitored. chemical changes in the urine, leading to Hertfordshire, AL4 8AN the formation of struvite. 8 Huntingdon Life Sciences, Breast cancer is the most common cancer Woolley Road, Alconbury, in women, with over 40,000 cases diag- As a result of these side effects, we altered Huntingdon, Cambridgeshire, nosed every year in the UK alone. As E our project licence to include the forma- PE28 4HS is known to be the most potent stimulant tion of struvite as a possible adverse effect, for breast cancer growth, many current ensured that animal care staff monitored Summary drug therapies aim to oppose the effects animals with E-pellets very closely and of E (e.g. tamoxifen) or prevent it from obtained veterinary advice on observing The RSPCA/UFAW Rodent Welfare Group forming (e.g. aromatase inhibitors). Our clinical signs and setting humane end- holds a one-day meeting every autumn so studies use xenograft models generated points. It is quite clear that there must that its members can discuss current wel- in athymic nude mice to investigate the be some level of pain suffered by affected fare research, exchange views on rodent action of such E opposing drugs. The mice animals and it is essential that discomfort, welfare issues and share experiences of are ovariectomised and, after a recovery pain and distress are effectively detected the implementation of the Three Rs of period of at least 7 days, implanted subcu- and assessed. replacement, reduction and refinement taneously with slow release E-pellets. This To this end, we have developed a simple with respect to rodent use. A key aim of maintains E at clinically relevant doses. 6-point guide to detecting the presence of the Group is to encourage people to think Mice are then injected subcutaneously struvite in mice with E-pellets: about the whole lifetime experience of with human breast tumour cells, which laboratory rodents, ensuring that every take two to four weeks to form a tumour potential impact on their wellbeing has approximately 7 mm in diameter. The W weight loss, which is an early been reviewed and refined. animals are then randomised to receive indicator and can occur quite the various therapies under study. suddenly; Presentations at the 2007 meeting includ- A abdominal distension, as a result ed refining procedures in breast cancer During the course of our studies we of fluid retention and swollen and gut pathogen research, refining stud- observed that two to three weeks after bladder;

46 Volume 8, No. 2 | february 2008 www.labanimaleurope.eu meeting REVIEW Report of the 2007 RSPCA/UFAW Rodent Welfare Group meeting (cont)

S skin colour changes; mouse strains are highly susceptible to These are listed below. H hydration is poor, leading to systemic infection. There are a number of poor skin condition; different approaches that can be taken to • Treating mice with antibiotics, so that U urethra irritation, where animals reducing suffering and improving welfare they develop an enteritis-like disorder, drag their hindquarters on the in mouse models of salmonellosis. which is more clinically relevant1. substrate and skin irritation and • Using less susceptible strains, such as reddening are apparent; A key area of interest at the Rowett C3H/HeN2. P palpation of lower abdomen Research Institute is the study of the roles • Housing in pairs. We use male reveals the presence of calculi. of bacteria, including pathogens, in mod- or female mice, aged 7 to 8 weeks and ulating gut development and function and weighing at least 19 g. Besides the This “WASHUP” system has proved to be long-term health. We have been conduct- welfare benefits of avoiding single easy to use and remember and has greatly ing studies on Salmonella enteritidis and housing, we have found that there helped us to refine our endpoints and typhimurium and the role of virulence are implications for our experimental reduce suffering. factors in modulating the early stages of results. Singly housed mice do as well infection for some years (virulence factors: as pair-or group-housed mice if they There are a number of other options molecules produced by a pathogen that are healthy or have a low level of that we are considering to avoid wel- specifically influence their host’s function, infection, but singletons do far worse fare problems with E-pellets. We have thus allowing the pathogen to thrive). if they have significant infection. We successfully genetically modified some of Most of this work was done in , where assume that data are less likely to be our tumour cell lines so that they can a self-limiting gastroenteritis-like disorder applicable from singly housed mice, be grown under androgen support when develops which is similar to the common due to the physiological effects of implanted into the mice, which avoids the form of infection in humans. However, isolation stress. If mice are left alone need for E-pellets. We have also refined the emphasis has recently moved to study- because a member of a pair has our procedures for this model so that ing the role of the innate and adaptive reached an endpoint, we re-house the time taken for tumours to develop is immune system in controlling gut-bac- them with counterparts at the same reduced, in turn decreasing the incidence terial interactions in the short and long stage of infection wherever possible. of urinary calculi. These modifications term. This requires changing from the • Supplying tunnel inserts in include removing the E-pellets early, using to a mouse model of salmonellosis, metabolism cages for short term alternative methods of administering E or because the necessary immune reagents studies (Fig. 1). This provides them commencing the therapy regime earlier and probes are currently available for mice with a secure nesting area and they whenever possible. In addition, we con- but not rats. keep the tunnels very clean so there stantly review the literature on struvites are no problems with faeces or urine in humans to see whether any equivalent Although mice are widely used in the collection. It also helps with handling therapies can be used in animals. For study of salmonellosis, the infection trig- because the mice can be lifted out example, antibiotic therapy has not been gered in most mouse strains is atypical and while they are in the tunnels. ruled out but any potential effects on lethal, in contrast to the rat. The stand- • Providing powdered, semi-synthetic tumour models and therapies would have ard strains used are Balb/c or C57Bl/6, diets (used in short term studies) in to be carefully evaluated. which are highly susceptible to systemic the form of freeze-dried blocks, so infection. Oral or i.p. infection with that the mice still get to gnaw on their Refinements in the management and Salmonella typhimurium leads to uncon- food. short- and long-term monitoring of trolled proliferation and bacteraemia. This • Not fasting the mice before afternoon pathogen-infected mice resembles typhoid-like disease in humans dosing, as we have found that they eat but is atypical of the infections caused little during the day. We withdraw George Grant, Gut Immunology Group, by S. enteritidis or S. typhimurium in food at around 11:00 and dose the Rowett Research Institute, Greenburn Road, most domestic animals and humans, mice at around 15:30. Bucksburn, Aberdeen, AB21 9SB raising doubts as to the appropriate- • Avoiding gavage when carrying out ness of the model. This is also a con- oral dosing by adding the bacteria or It has recently become necessary to move cern on animal welfare grounds, so we bioactive compound to a carrier that from using rats to mice in salmonellosis have set up a number of measures that the animals will eat voluntarily. This studies, for scientific reasons, but this has we use whenever possible to reduce or works even for anaerobic bacteria. led to welfare problems because many avoid suffering. Mice prefer agar or potato starch

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paste spiked with oil, whereas environment and (ii) health and welfare R6/2 mice are already provided with paper rats like jelly or chocolate drops. monitoring will be enhanced if nest build- wool nesting material as standard, but we Intake is usually rapid (one to ten ing ability is taken into account. wanted to investigate nest building behav- minutes) but can depend on the time iour in more detail. We conducted a study of day in mice; we have found it Huntington’s disease (HD) is a progres- in three parts to assess; (i) nesting behav- best to dose them early in the sive, inherited neurodegenerative disorder iour in R6/2 mice, (ii) the effect of differ- evening. Alternatively, suckling or for which there is currently no treatment. ent nesting materials on nest quality and newly weaned mice are dosed by It is characterised by movement abnor- mouse body weight and (iii) the effect of dropping very small volumes onto malities (a chorea with uncontrollable increased environmental temperature on the mid/back of the tongue using a jerking and writhing movements), cogni- weight loss. Part (iii) relates to the decline milk-based carrier and micropipette tive impairment and emotional distur- in body weight from 10 to 12 weeks with a round-ended tip. This can take bance. There are ten different mouse in R6/2s; we wondered whether warmer several minutes. Gavage is used only models of HD. One of the models that ambient temperatures would result in a when a single, precise dose is needed. we use is the R6/2 strain, which shows a decrease in weight loss. The study will • Housing mice in standard cages with progressive neurological phenotype with be written up for publication in full else- solid floors for long term studies. abnormalities in motor function apparent where and is summarised below. Faeces and urine are collected from 5 weeks and cognitive deficits from during weighing, which does not 3.5 weeks. R6/2 mice show a progressive Nesting behaviour allow fully quantitative measurements weight loss from 9 to 10 weeks and usually but still provides good information die aged between 16 and 20 weeks. Groups of 5 mice were placed in clean about trends in bacterial excretion. cages with corn cob substrate and 10 g • Implementing humane endpoints by We were interested in studying the effects paper wool bedding shaped into a tight weighing and health scoring mice of environmental enrichment on nest ball. A red perspex “igloo” house was twice daily throughout a study and building behaviour in R6/2 mice. Enrich- placed in half of the cages. We used sixteen having a set of endpoint criteria ment has been found to modulate the groups of male mice aged 12 to 14 weeks (based on the health score and weight course of phenotype progression in sever- (8 wild-type and 8 R6/2) and eight groups change) that trigger immediate al animal models of neurological disorders of female mice aged 14 weeks (4 wild type removal of an animal from study. including Alzheimer’s disease, Parkinson’s and 4 R6/2). Nest building behaviour was Animals are allocated a health score disease and HD, and has been shown to quantified at 30 minutes, one hour and 3 based on Shu et al. (Box 1). The slow disease progression in R6/2 mice4,5. 18 hours after the mice were placed in the endpoint is a score of 2 or above plus Environmental stimulation for humans cages. The nests were scored as follows; weight loss over 4 successive with HD, in the form of “remotivation 0 = nesting material unmodified, 1 = flat weighings. therapy”, has also been shown to improve nest with no assembled walls, 2 = shallow 6 Effects of environmental enrichment on functioning . nest lacking fully-formed walls, 3 = nest nesting behaviour and weight loss in a with well-developed walls and 4 = “coc- mouse model of Huntington’s disease There are a number of housing refine- coon” nest with partial or complete roof. ments that we provide for our R6/2 mice The height of each nest was also measured Pauline Burgun, Dr Dervila Glynn, Dr AJ to help them to cope with their disabling after 18 hours. House and/or nest use Morton, Dept of Pharmacology, University phenotype. They can find it difficult to was quantified by counting the number of of Cambridge, Tennis Court Road, Cam- reach the hard pellets in the hopper and mice in the house or nest (where present) bridge, CB1 1QJ drink from standard water bottles, so we at each of the time points. give them supplementary feed in the form Rodents with neurological disorders may of mash made from 100 g dry food soaked All of the mice built nests, but there were 7 have difficulty in manipulating some nest- in 230 ml tap water . We also provide some differences in nest quality. Wild ing materials, and their ability to build lower water spouts. Mixed phenotype type (WT) females had built better quality nests can also deteriorate in the case of housing, where R6/2 mice are housed with nests than WT males and R6/2 males at 18 some progressive diseases. Setting up wild-type cage mates, has also proven to hours (P < 0.05). R6/2 females were slow- studies to evaluate the type of nesting increase body weight and survival. The er to begin nest building, but there was no materials that particular strains prefer can wild-type mice groom and rest with the difference in their nest quality scores at 18 provide welfare benefits, in that (i) animals R6/2 mice, presumably providing both hours when compared with WT females. will be able to create a more comfortable comfort and stimulation. In females, nest height was not influenced

48 Volume 8, No. 2 | february 2008 www.labanimaleurope.eu meeting REVIEW Report of the 2007 RSPCA/UFAW Rodent Welfare Group meeting (cont)

by the presence of a house, but both WT ful consideration should be given to the opments in these areas that can improve and R6/2 males built higher walled nests use of wood wool for transgenic mice. the welfare of animals used in biotelem- when housed without one. At 18 hours, The study also highlighted the importance etry studies. all of the female WT and R6/2 mice were of evaluating different nesting materials using their nests and houses and so were for different strains. Biotelemetry provides the ability to mon- most of the male mice, although fewer itor key physiological parameters such R6/2 males with igloos were inside them. Increased environmental temperature as core body temperature (Tc) in unre- To conclude, although we know that nest strained subjects, which has widespread building ability deteriorates with time in A heated chamber was constructed with implications for improving scientific R6/2 mice, the key difference at 12 to 14 clear, perspex walls secured to a metal validity and providing objective measures weeks lies in the females’ latency to start floor with a water inlet and outlet. The of welfare. At present, the physiologi- building. chamber was placed in a standard mouse cal burden associated with biotelemetry cage and connected to a water bath that precludes its routine use in small animals Different nesting materials maintained its floor at a constant 37 oC. for measuring parameters such as Tc, Mice were housed in the cage containing although temperature modulation of indi- Groups of 10 female R6/2 mice, aged 10 the chamber in groups of 7 and were free viduals and their social group is arguably weeks, were assigned to three treatments; to choose whether or not they entered the of particular importance in behaviour and (i) paper wool, (ii) sizzle nest or (iii) wood chamber. A control group (N = 7) was welfare studies. wool. Nest building was assessed daily by housed in a standard cage with a red per- Also, traditional biotelemetry systems are scoring nest quality and height as above, spex igloo. All mice were weighed twice generally only able to monitor one ani- then calculating a weekly average score. weekly between 9 and 20 weeks. mal at a time within a given arena due to Body weight was recorded twice weekly “cross-talk” between devices transmitting until the study ended at 22 weeks. Increasing the environmental temperature on the same frequency. This can present did not have an effect on delaying weight a dilemma because, while single housing The mice with paper wool became more loss in R6/2 mice. The R6/2 mice preferred for mice should be avoided, there is also competent at nest building but could not to nest in the heated chamber, but this had an imperative to maximise the data col- form a grade 4 nest. They could not build a deleterious effect on their survival. In lected from all animals. Possible solutions a nest with walls at 22 weeks. None of the part, this may have been because by stay- are the “buddy” system, where animals mice could build grade 4 nests with wood ing in the chamber, they did not engage in are pair housed and only one individual wool; the best attempt was a doughnut- normal behaviour in their home cage. On is implanted8, but an ideal biotelemetry shaped grade 3. Later stage R6/2 mice this basis, it appears to be better to allow system would be able to record from all were incapable of building adequate nests R6/2 mice to create their own microenvi- animals in an arena. From an animal wel- with wood wool at all. Interestingly, the ronment by providing appropriate nesting fare aspect, devices should also be as small mice became better at building with sizzle material than to supply supplementary and light as possible, require less power nest as they got older. heating. (therefore a smaller, lighter battery), be able to monitor multiple parameters and New insights using telemetry: refining Changes in the progressive deterioration have decreased surgical requirements9. in body weight observed in R6/2 mice endpoints and the value of group housed were also dependent on the nesting mate- data A recent development in biotelemetry rial used (P < 0.001). All the mice gained technology, the Remo 400 series, enables weight normally up to approximately 15 Paul Ashley, Remo Technologies Ltd, Build- Tc to be continuously and remotely moni- weeks, then their weights remained rela- ing 227, Porton Down Science Park, Salis- tored in up to 16 group-housed individu- tively constant between 15 and 18 weeks bury, Wiltshire, SP4 0JQ als, without “cross talk” (www.remotech- (17 weeks in the case of the wood wool nologies.com). The device weighs under 1 group). All of the mice then began to lose Two key welfare issues associated with the g because it has no battery and is suitable weight. The group with the wood wool use of biotelemetry are implant size and for mice and larger animals. Body tem- lost most weight by the end of the study the practice of singly housing animals to perature follows a stable circadian rhythm and the group with the paper wool lost the avoid “cross talk” between devices that by the third day following implantation least. We concluded that sizzle nest should transmit on the same frequency. Telem- surgery. Preliminary studies suggest that be the nesting material of choice for mice etry device design is a rapidly developing this time to recovery of circadian rhythm with neurological disorders and that care- field and there are a number of new devel- is shorter using these implants when com-

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pared to other, heavier devices10. Also, Tc due to better quality data. This technol- cal training given to technicians. measured in group housed mice is signifi- ogy can also be used to gain better insights cantly higher, during both the light and into animal behaviour, refine humane Therefore, I embarked on a one month dark phases, than that described previ- endpoints and maximise the information intensive training and work experience ously in singly housed animals maintained obtained from each individual, making placement at the German Mouse Clinic under similar environmental conditions. every single animal count. (GMC) (www.mouseclinic.de) in order to gain the knowledge and technical skills Previously unobtainable information on Learning genetically altered mouse phe- required to perform standardised phe- multiple animals within a social group notype testing: training at the German notype tests through to tertiary level. can now be recorded and social species Mouse Clinic The GMC opened in 2002 and has a taking part in certain studies involving purpose-built phenotyping centre with a biotelemetry can now be maintained in Clare Millum, Cancer Research UK, PO high-throughput system that evaluates a an appropriate setting, gaining maximum Box 123, Lincoln’s Inn Fields, London, number of parameters including pathol- formation from all animals 11,12,13,14. WC2A 3PX ogy, behaviour, neurology, morphology, clinical chemistry and cartilage and bone Biotelemetry can be especially useful when As the use of genetically altered (GA) mice formation. Training consisted of pheno- studying infectious diseases, particularly continues to increase, it is essential that typing theory, practical work experience, in bio-containment, where the require- all relevant staff are adequately trained lectures and discussions, data handling ment for minimal human contact can in phenotyping and welfare assessment and statistics and the use of videos. We create problems with monitoring disease so that both expected and unexpected had hands on experience performing phe- progression and implementing humane adverse effects can be effectively detected, notyping tests, including with strains that endpoints. Telemetry has been success- assessed and alleviated. had very unusual phenotypes. (During fully used to these ends in studies involv- the discussion, it was pointed out that a ing the characterisation of the response For example, Cancer Research UK (CRUK) UK training course is also available at the to toxic challenge and the assessment of has over 300 GA mouse lines produced in Council’s Lyon vaccine efficacy. In projects such as these, house, with a total of over 500 crosses. Of Centre, Harwell; www.mlc.har.mrc.ac.uk) it has been found that changes in Tc these lines, 60 are known to have adverse can occur before behavioural changes or phenotypes that affect the welfare of the The training and knowledge that I gained clinical signs can be detected by simple mouse. Many more are suspected to have from the work experience placement will observation. This can provide objective mild, moderate or neurological/behav- be used to launch a mouse phenotype data to enable the refinement of humane ioural phenotypes that have not been fully passport system at CRUK. It is hoped endpoints. It can also detect the onset of identified to date, yet may still impact on that the passport system will bring about infection, so that animals can be moni- welfare. many welfare advances and bring to light tored more closely or given additional any previously unknown phenotypes care. For example, using this telemetry Projects such as EUMORPHIA (www. that affect mouse welfare. In particular, it technology, Tc changes following dis- eumorphia.org) and Europe-wide phe- should help to identify and record strain- ease challenge have been found some 11 nome projects have been catalytic in the specific needs with respect to handling, hours before any behavioural changes and increased popularity of mouse passport husbandry and general care, improve vet- 13.5 hours before the onset of clinical systems. Imminent plans for the expansion erinary care and establish specific humane signs of disease14. Other studies have now of CRUK’s main mouse facility mean that endpoints for adverse phenotypes. described Tc response to viral infection in house production is expected to more in rodents in their normal social environ- than double. At least 60 lines are already Sourcing rodents from overseas ment11. This is particularly significant known to have adverse phenotypes, and when considering the differences in ther- we are expecting to encounter more as our Robert Hubrecht, UFAW, The Old School, moregulation observed between group facility expands, so the need for pheno- Brewhouse Hill, Wheathampstead, and singly housed mice. type identification and a mouse passport Hertfordshire, AL4 8AN scheme at CRUK has become increasingly In conclusion, advances in biotelemetry apparent. Accuracy and standardisation Refinement includes the entire birth to technology have clear implications for the of phenotype testing will be key to their death experience of every animal, includ- Three Rs in relation to reduced device bur- success. The specialized training required ing breeding and sourcing. Most animals den, the potential to group house and the to perform such tests is often out of the used for research and testing in the UK are possibility of reducing animal numbers realms of standard husbandry and techni- bred within the UK. However, if the spe-

50 Volume 8, No. 2 | february 2008 www.labanimaleurope.eu meeting REVIEW Report of the 2007 RSPCA/UFAW Rodent Welfare Group meeting (cont)

cies, strain or type of animal is not avail- As a minimum, data should be collected When using rodents in regulatory studies, able, they may be imported from abroad. on health status, any health issues, social there is much that can be done to promote There are a number of measures that housing, provision of enrichment and the implementation of the Three Rs establishments can take to help ensure the whether the supplying institution among clients and regulatory bodies. I welfare of imported animals before they meets (or exceeds) relevant national or am currently Section Manager for the reach their end destination. professional standards. Ideally, importers Rodent Division at Huntingdon Life and users should visit the supplier or Sciences. I have worked in contract and In the case of rodents, conventional look at photographs or videos to satisfy pharmaceutical research since 1987 and animals generally come from well known themselves that appropriate standards are the following is based on my experiences breeders, but it is not known how being met. The information can be judged as Facility Manager within a barrier much information relevant to housing against guidelines such as the current facility with thirty animal rooms housing and husbandry is routinely collected by UK husbandry standards for breeders16 Specific Pathogen Free (SPF) rodents. importers. There are many other potential or the recent revision of Appendix A Studies are carried out predominantly sources of genetically altered animals and to European Convention ETS12317. under a toxicology and oncology project it is difficult – if not impossible – for the Alternatively, institutions may prefer to licence, involving acute, neurological UK Home Office Inspectorate to influence use their own guidelines for good practice, and reproductive toxicology through to them or even know who they all are (the if these improve upon the relevant legal lifetime carcinogenicity studies in rats and Home Office Inspectorate implements the minimum standards18. mice. law regulating animal use in the UK, the Animals (Scientific Procedures) Act The Committee recommends that I have encountered a number of 1986). institutional Ethical Review Processes issues relating to animal welfare and (ERPs, which review the implementation environmental enrichment over the last In view of this, the Housing and Husbandry of the Three Rs at a local level and are 20 years, and we have been able to make Sub-Committee of the Animal Procedures mandatory in UK establishments) should significant progress in ensuring that the Committee (APC; www.apc.gov.uk) ensure that mechanisms are in place “to Three Rs are realised and that animal has published a document that reviews monitor and record health and previous welfare and enrichment is prioritised. My current practice and provides additional housing or husbandry issues that could staff have been able to collect significant recommendations for importing animals affect the welfare of imported animals data over a five-year period that allows that should be obtained from a designated and the quality of science derived from quantification of some very tangible breeding establishment under UK them”. The Committee also recommends benefits. Three of the areas in which we legislation15. that “the aggregated information collected have helped to introduce positive change by ERPs should be reviewed at a National are set out below. The APC report recommends that level within two years”. A key aim of importers and users should continue the review would be to check that the “Spare” animals and effective animal to collect data on the health status of process collecting and reviewing data usage imported animals. It also recommends from overseas suppliers is robust enough that they should seek information from to ensure good health and welfare, and to We aim to reduce the number of “spare” the supplier on the welfare and standards determine whether any revisions may be animals ordered and we record all of housing and husbandry for all imported necessary. instances of no-use in order to promote species, including rodents, that are listed in alternative usage. Data on “spares” and Schedule 2 of the UK Animals (Scientific The full APC report is available at http:// no-use is reported to the ERP quarterly. Procedures) Act 1986. (This Schedule www.apc.gov.uk/reference/2007-0404- The number of “spare” animals not used lists species that may be obtained only web-version-standards.pdf fell to zero once we started having to report from designated breeding or supplying to the ERP, so it has been very influential establishments.) Some researchers already Championing animal welfare in in reducing wastage. Animals surplus exceed the current minimum regulatory toxicology to study requirements are now used for requirements for imported animals, other purposes, e.g. to provide blood by obtaining information on animal Kevin Curtis, Huntingdon Life Sciences, products for equipment validation or to welfare and husbandry conditions from Woolley Road, Alconbury, provide tissues for training in necropsy their overseas suppliers. The APC Sub- Huntingdon, Cambridgeshire, and histology. Some are released from the committee commended this as good PE28 4HS Act and re-homed as companion animals. practice.

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Individual housing Box 1. Health score system for Group housing is our standard; five rats Salmonella studies3 per cage or trios for mice. Any require- ment for single housing must be author- 1. Bright eyed, alert, smooth ised by the Named Veterinary Surgeon and coat, inquisitive Named Animal Care and Welfare Officer 2. Fur slightly ruffled but active (NVS and NACWO; two posts required and alert under UK law) before studies begin. 3. Ruffled/clumped fur, reduced activity, hyperventilates There are some exceptions on veterinary 4. Hunched and sleepy, fur or welfare grounds, such as some surgi- clumped, little interest cally prepared animals, dermal studies and Hunched, very sleepy, non- male mice of specific strains. However, Figure 1. Tunnel insert for use in metabolism cages responsive, cold some clients have traditional preferences for single housing. We always challenge Environmental enrichment this and encourage them to comply with cology studies, but these can usually be our welfare policy; they often agree to Welfare issues confronted in rodent toxi- overcome. For example, there are concerns group housing for their animals. We cology mainly relate to ageing animals, about the lead content in cardboard “fun have also challenged the requirement for boredom and stereotypic behaviour. tunnels”, especially as rodents chew and single housing in the US Food and Drug Animal technicians are encouraged to eat them. We use perspex “fun tunnels” Administration “Red Book” regulations provide and research ideas to tackle all instead, which come with a Certificate of for food additive tests, but unfortunately of these issues, such as environmental Analysis, do not have a high lead content unsuccessfully to date. We also have to enrichment, and all such initiatives are and are also autoclavable and reusable. report the percentage of animals individu- reported to the ERP quarterly. We use perspex houses and “igloos” for ally housed to the ERP and, again, the ERP our rodents. has been influential in increasing account- There may be issues associated with pro- ability and bringing the numbers of singly viding some types of enrichment on toxi- Keeping up with challenges housed animals down (Fig. 2). We are committed to pushing the bounda- ries and championing welfare initiatives, but there are some challenges that require due consideration. Our ongoing challeng- es are: • Trialling new products to ensure that enrichment does not introduce other variables that may compromise study integrity • Coping with clients’ requests for novel techniques or procedures • Clients’ differing receptiveness to environmental enrichment • Continued commitment to the review of current techniques and procedures so that refinements are implemented wherever possible • Continuous review of Certificates of Analysis

We involve and inform Business Develop- ment with respect to all of the above proc- Figure 2. Decrease in the percentage of animals individually housed in a rodent toxicology esses and we educate everyone about our facility following reporting to the ERP

52 Volume 8, No. 2 | february 2008 www.labanimaleurope.eu meeting REVIEW Report of the 2007 RSPCA/UFAW Rodent Welfare Group meeting (cont)

welfare policy and the reasons behind it. Environmental enrichment slows disease 12. Mann T, Griffiths G, Scott L, Ashley P All NACWOs must make a presentation to progression in R6/2 Huntington’s disease (2007) Development of humane endpoints the ERP every year about our welfare ini- mice. Ann. Neurol. 51: 235-42 in ricin inhalation toxicology. Poster pres- tiatives and refinements to husbandry and 5. Nithianantharajah J & Hannan AJ entation at Society of Toxicology meeting, procedures. In this way we can all work (2006) Enriched environments, experi- North Carolina, March 2007 together to promote better standards for ence-dependent plasticity and disorders 13. Teeling J, Felton L, Deacon R, animals in toxicology. of the nervous system. Nat. Rev. Neurosci. Cunningham C, Rawlins J & Perry VH 7: 697-709 (2007) Subpyrogenic systemic inflamma- Acknowledgements 6. Sullivan FR, ED, Alpay M & tion impacts on brain and behaviour, Cha JH (2001) Remotivation therapy and independent of cytokines. Brain Behaviour The Group would like to thank all of the Huntington’s disease. J. Neurosci Nurs. 33: and Immunity 21: 836-50 speakers and everyone who attended and 136-42 14. Williamson ED, Savage VL, Lingard participated on the day. Many thanks to 7. Carter RJ, Hunt MJ & Morton AJ B, Russell P & Scott EA (2007) A biocom- Cancer Research UK at Cambridge for (2000) Environmental stimulation patible microdevice for core body temper- providing us with a meeting venue, espe- increases survival in mice transgenic for ature monitoring in the early diagnosis of cially to Paul Mackin who organised it all. exon 1 of the Huntington’s disease gene. infectious disease. Biomed. Microdevices Mov. Disord. 15: 925-37 9: 51-60 References 8. Hawkins P, Morton DB, Bevan R, 15. APC (2007) Consideration Of Heath K, Kirkwood J, Pearce P, Scott E, Policy Concerning Standards Of Animal 1. Barthel M, Hapfelmeier S, Quintanilla- Whelan G, Webb, A. (2004) Husbandry Housing And Husbandry For Animals Martínez L, Kremer M, Rohde M, Hogardt refinements for rodents, dogs and From Overseas Non-Designated Sources. M, Pfeffer K, Rüssmann H & Hardt WD non-human primates used in telem- http://www.apc.gov.uk/reference/2007- (2003) Pretreatment of mice with strep- etry procedures. Laboratory Animals 0404-web-version-standards.pdf, accessed tomycin provides a Salmonella enterica 38: 1-10 16 November 2007 serovar Typhimurium colitis model that 9. Morton DB, Hawkins P, Bevan R, 16. Home Office (1989) Code Of Practice allows analysis of both pathogen and host. Heath K, Kirkwood J, Pearce P, Scott E, For The Housing Of Animals In Designated Infect. Immun. 71: 2839-58 Whelan G, Webb A (2003): Refinements in Breeding And Supplying Establishments. 2. Hawkins P, Grant G, Raymond R, telemetry procedures. Laboratory Animals London: HMSO Hughes G, Morton D, Mason G, Playle L, 37: 261-99 17. Council of Europe (2006) Appendix Hubrecht R & Jennings M (2004) Reducing 10. Ashley PJ, Mann T, Williamson D, A Of The European Convention For The suffering through refinement of proce- Felton L, Scott L & Schnell C (2007) Protection Of Vertebrate Animals Used dures: Report of the 2003 RSPCA/UFAW Remote monitoring of core body tem- For Experimental And Other Scientific rodent welfare group meeting. Animal perature in multiple mice within a social Purposes (Ets No. 123): Guidelines For Technology and Welfare 3: 79-85 group. Poster presentation at LASA winter Accommodation And Care Of Animals 3. Shu Q, Lin H, Rutherfurd KJ, Fenwick meeting 2006, Glasgow and FELASA-Iclas (Article 5 Of The Convention). Strasbourg: SG, Prasad J, Gopal PK & Gill HS (2000) meeting, Como, 2007 Council of Europe. Dietary Bifidobacterium lactis (HN019) 11. Cunningham C, Campion S, Teeling J, 18. Jennings M, Batchelor GR, Brain PF, enhances resistance to oral Salmonella Felton L & Perry VH (2007) The sickness Dick A, Elliott H, Francis RJ, Hubrecht typhimurium infection in mice. Microbiol behaviour and CNS inflammatory media- RC, Hurst JL, Morton DB, Peters AG, Immunol. 44: 213-22 tor profile induced by systemic challenge of Raymond R, Sales GD, Sherwin CM 4. Hockly E, Cordery PM, Woodman mice with synthetic double stranded RNA & West C (1998) Refining rodent B, Mahal A, van Dellen A, Blakemore C, (Poly I:C). Brain Behaviour and Immunity husbandry: The mouse. Laboratory Lewis CM, Hannan AJ & Bates GP (2002) 21: 490-502 Animals 32: 233-59 Tables and figures.

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