f6098d8b__and_Use_of_Laboratory_Animals__Comments
[ID] 5 [Entry Date] 02/25/2011 at 02:10:54 PM [Affiliation] Organization [Organization Name] IACUC, University of Virginia [Organization City and State] Charlottesville, VA [Comments] 
Comment 1: I would like to thank the "Committee to Update the Guide for the Care and Use of Laboratory Animals" for its thoughtful and thorough undertaking in updating and comprehensively making additions to the 2010 "Guide." This was undoubtedly a daunting challenge for which you are all to be commended. Our Institutional Animal Care and Use Committee has reviewed the pre-publication version of the 2010 "Guide" and would like to express our concerns on only two changes. One change we feel will adversely impact the biomedical research community, and on the other hand proposes something that is at odds with experts in human medicine. The first issue pertains to the need to provide a female mouse with litter 50 sq. in. of cage floor space (page 62). Currently the most common type of mouse caging at our institution is a small shoebox that has a floor space of 75 sq. in. allowing housing five adult mice similar, I'm certain, to many other institutions. The caging industry has built the small shoebox cage to this floor size standard based upon the 1996 "Guide." The most common mouse breeding scheme at our institution is the polygamous trio harem of one male and two females established to maximize rodent production by taking advantage of the post-partum estrus and the cross-fostering of litters by two resident lactating females. Our IACUC's concern regarding overcrowding in harem breeding cages led to our policy that states "no more than 12 pups when the older of two litters reaches 12 days of age".1 This requires one pregnant prepartum female be removed when large litters are the result of this mating. But given that the vast majority of our mouse colonies are genetically-engineered mice (GEMs) with a propensity to have small litters, similar to many inbred strains of mice, we have anecdotal evidence that the presence of two lactating females increases the probability of offspring maturing to weaning; the reproductive success at weaning being our measure of the well-being of the offspring. To our knowledge there is little evidence in the literature of GEM offspring well-being adversely impacted by trio breeding. If this requirement is implemented it would cause a substantial increase in the number of shoebox cages we currently would have to maintain and impact the mouse space available to support our current research programs. However, given the current language in Table 3.2 of the new "Guide" all trios would be required to be separated precluding the possibility of cross-fostering of small litters. I ask that you consider removing this space requirement for female mice with litters from the 2010 "Guide" and allow each institution to develop a policy similar to our own (attached). The other issue our IACUC feels should be re-examined is the requirement for oxygen sensors in animal magnetic resonance imaging areas where cryogenic gases are used (page 157). The literature sited for this requirement appears in the ILAR Journal.2 We respect the opinion of the authors but find them at odds with the American College of Radiologists (ACR) Guidance Document for Safe MR Practices: 2007.3 The ACR guidance document specifies cryogen emergency vent locations and pathways, and specifically states on page 12, "It should be pointed out that room oxygen monitoring was discussed by the MR Blue Ribbon Panel and rejected at this time because the present oxygen monitoring technology was considered by industry experts not to be sufficiently reliable to allow continued operation during situations of power outages, etc." When a significant cryogen quench occurs that would decrease room oxygenation the room rapidly fills with fog, the location of the exhaust vent away from the exit door, signage stating to exit the room when this occurs and appropriate vent piping and placement of the discharge point are the most important safety factors according to the ACR. Our IACUC further feels that specifying the use of non-ferrous compressed gas tanks around MR scanners rather than remote storage would seem prudent. I hope the committee will consider our IACUCs collective opinion with regard to these two new requirements of the 2010 "Guide." We feel it our responsibility to inform the Committee to Update the Guide for the Care and Use of Laboratory Animals of our sentiments. Sincerely yours, William Sutherland, PhD Professor of Cell Biology Chair, Institutional Animal Care and Use Committee University of Virginia 1. ReebWhittaker et al. 2001. Laboratory Animals 35:5873 2. Klaunberg BA, Davis JA. 2008. ILAR J 49:4-16. 3. E. Kanal et al. 2007. AJR 188:1–27 Comment 2: POLICY ON BREEDING AND WEANING OF RATS AND MICE Federal regulations establish the density of animals permitted in rodent cages. Breeder rats and mice and their litters can occupy considerable cage space, produce large amounts of fecal and urinary material, and increase cage temperature, humidity, and ammonia levels, all of which can create unhealthy conditions. When litters of two different ages are present in the same box, the younger litter often receives insufficient milk. Finally, the presence of more than one male in a breeding cage often results in aggression between competing males and fetal resorption (Bruce effect). The following standards provide allowable densities and age/sex combinations to be applied to mouse breeding cages. Special exemptions to these standards can be made that improve animal well-being, such as to accommodate weanlings of low birth weight, slow growth rates, or insufficient mothering; a typical solution might be to cross-foster to other females in the cage. Requests for ongoing exceptions for particular strains should be submitted to the ACUC by revision of your animal use protocol, in the Main Procedure section under a heading "Request for Exception to the Breeding and Weaning Policy". Exceptions must be justified by providing published citations or PI data demonstrating post-natal failure-to-thrive of the strain in question. Potential reasons for exemption(s) include: 1) Experimental design (e.g. studying psychological imprinting of pups); 2) Need to extend suckling in strains that fail to thrive (requires supporting data); 3) Need to prevent cannibalism diminished by cross-fostering (requires data). BREEDING SCHEMES AND LITTER NUMBERS ALLOWED: •No more than one adult male is allowed in a breeding cage. •Female rodents must be at least 6 weeks old before they are placed in a breeding cage with a male who is greater than 10 weeks of age. The only exception to this is superovulation of 3-4 week old female mice for collection of zygotes or embryos. •A cage is considered overcrowded if a new litter is born before the older litter from the same female is weaned, or if the older litter remains with the female beyond 23 days of age. Litters with ? 4 pups do not require weaning separation if the male is removed during pregnancy. •Weaning beyond 23 days (25 days of age if CCM does it) is reserved for strains that have litters that routinely fail-to-thrive. In such cases, the male, or even better the pregnant female must be removed from the cage when either female is obviously pregnant (e.g. by 12 days gestational age). Note: Late weaning of this sort requires a special exemption as defined below to avoid ACUC censure. Animal caretakers are responsible for recording birth dates for litters on cage cards, however they may be recorded by research staff as well. A. One male x one female: Litters should be weaned by post-natal Day 23, or before birth of another litter, whichever is first. Animal care technicians will automatically wean each litter by post-partum Day 25, or whenever a new litter is born, if investigators have not already done so. Investigators will be charged for this service. If there is no prior arrangement with the CCM staff to wean for the PI, it will be considered a non-compliance issue by the ACUC. B. One male x two females: If breeding is conducted in a 1:2 ratio, it is recommended that one of the two females be removed to a separate cage when observed to be pregnant*. Alternatively, it is permissible to keep the male, two females, and the pups together provided that when the oldest litter reaches 12 days of age there are no more than 12 pups in the cage (combined). This is based upon standards used at the Jackson Laboratory (Reeb-Whittaker et al, 2001, Laboratory Animals 35:58-73). Weaning must still be accomplished by Day 23. The animal care technicians will wean litters at Day 25 if not already done by the investigators, and investigators will be charged for this service. If there is no prior arrangement with the CCM staff to wean for the PI, it will be considered a non-compliance issue by the ACUC. C. One male x three or more females: If more than two females are housed with a male for breeding, pregnant females (e. g. 12 days gestational age*) must be separated into boxes containing no more than two pregnant females before any delivery, and the 1:2 policy above ("B.") is then followed. If removal of obviously pregnant females in this breeding scheme is not done by the research staff, the animal care technicians will perform this function and investigators will be charged for this service. If there is no prior arrangement with the CCM staff to wean for the PI, it will be considered a non-compliance issue by the ACUC. The accepted procedure for post-Day 25 day weaning: Occasionally, litters (or individuals in a litter) do not thrive or there may be other extenuating circumstances to justify delayed weaning. If you feel a litter (as defined in this policy) is not ready to be weaned, consult your vivarium supervisor. Each supervisor has the authority to provide a one-time exemption (one cage, or for concurrent cages of a new strain) delaying weaning up to 9 days in length for any specific litter (normally weaned on Day 23, extension to 32 days maximum). If a new litter is born to another female in the cage during the exemption period, it must be removed with that dam to another cage, if the original exempted litter cannot be weaned. Permission for ongoing weaning age exemptions for a particular breeding line must be obtained from the ACUC by submitting a protocol modification for that strain. Note: during any delayed weaning situation, the male must be removed from the cage when either female is obviously pregnant (e.g. by 12 days of gestation) to avoid post-partum estrus breeding.
Listing of Public Comments on Proposed Adoption and Implementation of the Eighth Edition of the Guide for the Care and Use of Laboratory Animals