Policies & Procedures

Cell lines and solid tumors present a major biological hazard to the animal facility. There are well known examples of rodent viruses being introduced into pathogen free colonies via tumors and/or cell lines. Pathogens such as mouse hepatitis virus, mycoplasma pulmonis, and lymphocytic choriomeningitis virus (LCMV) are pathogens of most concern. While most of the agents that are potentially found in rodent cell lines are species specific, there are documented cases of zoonotic agents also being introduced via tumors, such as hantavirus and LCMV.

Cell Lines

The materials of most concern are those derived from or passed through rodents (e.g., rats, mice, hamsters). The exact origin and propagation of human tumors/cell lines is often unknown or ambiguous, so it is important that investigators test all cell lines (regardless of origin) before using them in rodents. Until recently, the most reliable test was the mouse antibody production (MAP) test, where we inject samples of the suspect material into mice of various ages. WE then evaluated these animals for seroconversion to the rodent pathogens of interest. This process generally takes six to eight weeks. The IMPACT- PCR test shows similar sensitivity and specificity to the traditional MAP test for most agents. This method requires small amounts of material and is usually completed within two weeks. It has rapidly become the test of choice. If you need tumors or cell lines, contact the American Type Culture Collection, which is a nonprofit repository of cell lines. ATCC does not test any cell lines or tumors for rodent pathogens. This is the responsibility of the end user.

Primary Human Tumors

When researchers take tumors directly from patients, they rarely obtain enough cells to perform IMPACT testing. Often, researchers choose to place these materials into animals without the need for testing. Please note that you must follow bloodborne pathogens precautions when working with these materials. You must handle them under biosafety level 2 (BSL-2) conditions. Animals must be housed in an animal biosafety level 2 (ABSL-2) room.

Additional Information

For information as to how to get a cell line/tumor IMPACT tested, contact Ying Dai at 212-241-1696.

We follow the National Research Council recommendations on housing requirements for most animal species. It is the only reference for housing of laboratory rodents not regulated by the Animal Welfare Act . The most recent publication restricts the housing of mice to the following:

Caging density is based upon above housing guidelines and caging available at our facilities.

Annenberg and Atran Buildings Availability
Regular Allentown cage = 67.0 sq. in. of floor space:
Up to 25 grams – 5 adult mice per cage
>25 grams – 4 adult mice per cage

Allentown JAG cage = 75 sq. in. of floor space:
5 mice x 12 sq. in./mouse = 5 adult mice per cage

Hess Availability
Techniplast cages = 118.0 sq. in. of floor space
Up to 25 grams – 5 adult mice per cage
>25 Grams – 4 adult mice per cage

Icahn Medical Institute Availability
Allentown JAG cage = 75 sq. in. of floor space
Up to 25 grams, 5 mice x 12 sq. in./mouse = 5 adult mice per café
>25 grams – 5 adult mice per cage

We assume that most adult mice weigh 25 grams or greater. The National Research Council guidelines, however, do not adequately address the housing density for cages with breeding animals. We recommend the following housing densities for breeding colonies in all of our building:

• One female and litter up to 21 days of age
• One female and male with one litter up to 21 days of age
• Two litters in one cage (two generations or two separate litters will be considered overcrowding)

Reference: The Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, National Research Council, 2011.

Non-Approved Vendor Source Rodent Importation Policy

We consider sperm in-vitro-fertilization to re-derivation to be the preferred method of importing non-approved vendor mouse lines/strains onto campus. We offer this sperm service in partnership with the Mouse Generics Shared Resource Facility at a very competitive rate. We need two males (from 10 to 16 weeks and from 3 to 10 months of age) to carry out this procedure, which takes approximately 12 weeks (three weeks gestation, three weeks weaning). This timeframe includes breeding back to a single transgene zygosity and is comparable to that of our current whole animal quarantine program (12 weeks). The benefits of using the re-derivation route of importation are:

1. Eliminates the need for lengthy importation paperwork
2. Eliminates the risk of adventitious pathogens evading detection during quarantine
3. Assures that imported animals meet institutional health criteria post importation
4. Supports CCMS efforts to maintain a clean animal vivarium

If there are reasons that preclude the use of this re-derivation program, whole animal quarantine will be considered for importation (time alone is not a circumstance that would preclude the use of this program). Please note that the testing and length of surveillance is 12 weeks to allow for a thorough evaluation of the health status of the animals prior to release from quarantine.

In order to initiate the process of importing non-approved vendor source animals, please complete the our online Animal Shipping form

In completing the form, please note the background information and genotype (zygosity) of the animals you are requesting for re-derivation consideration. When we receive your Animal Shipping form, we will send a letter of approval with shipping dates for the animals requested along with a Mouse Genetics Shared Resource Facility (MGSRF) In-Vitro Fertilization re-derivation requisition form. Please complete this form so we can proceed with importing the animals for re-derivation. The use of the whole animal quarantine is pending approval of the exporting institution’s health report for the requested animals.

We receive and accept re-derivation shipments according to the MGSRF processing schedule. The schedule depends on appropriate weather conditions, as per World Courier policy (our preferred shipping courier). We accept shipments Tuesdays through Thursdays.

We conduct whole animal quarantine off-site at Charles River Laboratories (Wilmington, Massachusetts). Mice accepted into quarantine can be shipped directly to this site Mondays through Thursdays.

The CCMS shipping coordinator will provide the shipping address to exporting institute when our veterinarian provides approval of the whole animal quarantine.

We follow the Guide for the Care and Use of Laboratory Animals regarding housing densities for mice, particularly those involved in breeding protocols. Our husbandry procedure is to change mouse cages once weekly, based on the approved stocking densities. Overcrowding mice results in humane concerns as these animals are subjected to increased ammonia levels (urination), fecal contamination, and psychological distress.

When animals are found to be in overcrowded conditions, our staff members identify the cage with an “Overcrowded” card. Investigators then have 48 hours (Monday–Thursday) 72 hours (Friday–Sunday) (depending on the severity of overcrowding) to separate the flagged cages. We send notification of this flagging via email as a courtesy. However, the clock to correct the overcrowded condition begins running once the cage is flagged (not upon the courtesy email notification). If overcrowding is severe (multiple generations, multiple adults >10), the supervisor or veterinary staff reserve the right to separate the animals without notification. 

You may not remove the “Overcrowded” cards from the cages until you have addressed the problem. We will increase charges if the husbandry staff reports that cards were removed by investigators prior to separating cages that were reported as overcrowded. If investigators disagree with the need to separate animals, they should consult the IACUC to amend the protocol for this purpose. All litters over 21 days of age are considered overcrowded unless you have prior approval from the IACUC, which must specify the length of time of the extension. This information must be noted on a Special Services Requisition Form and posted within the room (i.e., “weaning at 28 days”).

Please note that repetitive non-compliance of this policy is considered an animal welfare issue and will be escalated to the IACUC for appropriate resolution.

Summary of Overcrowding Policy

1. Cage densities outside of approved housing guidelines will be flagged with an “Overcrowded” card
2. Courtesy Notification will be via email
3. Separation of reported cages must be done within 48 hours (Monday –Thursday), 72 hours (Friday- Sunday)
4. Cages not separated within three days of the initial flag will be separated by CCMS at charge of $52.50 for each reported cage
5. If the cards are removed without separating cages, the CCMS husbandry staff will separate the cages and charge $77.50 per new cage generated
6. Investigator must have prior IACUC approval to deviate from approved IACUC housing standards
7. Investigators may submit a Special Services Requisition for CCMS staff to separate overcrowded cages automatically without prior notification. CCMS will separate these cages at a fee for service. A Special Services Request must be on file for this service to apply.

Our policy is that rodents that undergo major surgery* must receive analgesics at induction of anesthesia (preemptive analgesia) and postoperatively for 24 to 72 hours. Typically, we recommend using buprenorphine HCL, given at 8 to 10 hour intervals for moderate to severe pain. You may use other agents, such as butorphanol, Tylenol, bupivacaine, and lidocaine, for minor pain, but these agents are limited by their duration of action (lidocaine, butorphanol) or difficulty of administration (Tylenol). Consult the veterinary staff if you have questions about choosing an appropriate analgesic.

*Note: Major Surgery is defined as procedures that penetrate and expose a body cavity or produces substantial impairment of physical or physiologic function. Ex. thoracotomy, craniotomy, limb amputation.

As investigator, the postoperative treatment of rodents is your responsibility. The IACUC requires proof of compliance during laboratory inspections, and the veterinary staff may request documentation of treatment when animals are reported for complications. Do not keep treatment records in animal rooms, to prevent them from being damaged or lost. We encourage you to make notations of treatments on the back of the "Rodent Surgery" cage card (see below), to assist the veterinary staff in assessing reported animals. The "Rodent Surgery" cage card is not sufficient recordkeeping. You must maintain some other permanent record in the laboratory (e.g., lab book or treatment form) in which you document all treatments and observations.

Postoperatively, investigators should place a "Rodent Surgery" card on each cage when returning the animals to the vivarium. Unless other arrangements are made with CCMS, it is your responsibility to administer treatments for a minimum 24 hours. You must observe the animals for a total of 72 hours, and then remove the "Rodent Surgery" card from the cage. Veterinary technicians monitor compliance during rodent rounds. We will observe animals with postoperative cards for signs of pain, wound infection, or other complications and we will notify you if there are any problems. Our veterinary staff will recommend a treatment plan.

"Rodent Surgery" cards are available in the facility supervisor office of the vivarium where your animals are housed. Please contact a member of the veterinary staff if you need assistance in evaluating postoperative pain in rodents.

1. Have the injured person follow the Mount Sinai Health Center Employee Health policy for Human Exposure to herpes simiae (herpes B virus) and identify the offending monkey. The policy is posted in all nonhuman primate housing areas. A member of the CCMS staff should accompany the injured person to Employee Health Service (EHS) with a copy of the EHS policy.
2. In all cases the offending nonhuman primate (NHP) should be examined by a veterinarian for lesions consistent with herpes infection. This includes New World primates and baboons.
3. In the case of New World primates or baboons, you must collect samples to submit to the lab since these animals harbor endemic herpes viruses which could cause disease in immunocompromised individuals.
4. If a person is injured by a macaque (M. mulatta or M. fascicularis) sustains a needle stick from macaque-contaminated needles or is splashed in the eye(s) or mucous membranes by fluid from a macaque, you must take cultures of the oral cavity, urogenital tract, and both eyes of the monkey. You must also collect acute serum samples. Swabs and culture media for culturing and viral transport are available in our diagnostic laboratory x4-1696 and in the Bite/Scratch Kits in each monkey room.
5. All samples from the NHP are to be packed in dry ice or ice pack and shipped priority overnight mail via Federal Express to the National Institutes of Health (NIH) Virus Resource Laboratory, Atlanta, Georgia.
6. Be sure to inform the NIH Virus Resource Laboratory requests of any sample shipments prior to sending them by calling them at 404-651-0808. You can also call this number for questions about the process.
7. Initiate a clinical record on the NHP involved at the time of processing, and place the NHP on clinical rounds for observation until you receive the serology and/or culture results (approximately 10 days).