1. Protecting the NCI Mouse Resource: Melody Roelke-Parker, DVM Laboratory Animal Sciences Program October 2015 NCI Mouse 101 Only limited pathogens are allowed and Rigorous importation quarantine Sentinel surveillance Strict guidelines for order of facility visits

2. Biosecurity is in ALL of our hands “NIH”

3. Extremely Valuable resource ~$23 per mouse $118 per cage $4,800 half Rack (Red Cards) C57BL/6J mice

4. Extremely Valuable resource C57BL/6J mice Bldg 10/CRC $600,000 for Athymic nudes 10 racks/room $160,000 for B6

5. Excluded pathogens Viruses Bacteria Parasites Imported Mice must be pathogen free Source of mice

6. APPROVED SOURCES

7. Germantown production facility ONLY Case-by-case review Source of mice APPROVED SOURCES

8. Ordering mice Different for NCI facilities and centralized facilities managed by DVR All orders placed by facility staff List the strain or stock, sex, number, age, delivery date, facility Must include PI, current ASP# and Center # Confirmatory email will be sent to ordering investigator Please be sure that name, contact info, and ASP # is accurate.

9. APPROVED SOURCES Source of mice Receiving and Quarantine Program at NCI-Frederick

10. Receiving Mice Approved sources are the Charles River Labs, Jax, & Taconic (Germantown only) Receiving and Quarantine Program at NCI- Frederick for most other sources Quarantine length 3.5-7.5 weeks Details and online forms at LASP website http://www.ncifcrf.gov/rtp/lasp/intra/randq/default.asp Mice may be moved by LASP staff between compatible facilities Health status is first reviewed by Facility Vet Recommended acclimatization: 5-7 days

11. Excluded pathogens at NIH Health status varies with the facility On the NIH Campus people and mice are allowed to move between facilities with similar health status – BUT MUST NEVER transit between a poorer health status and a higher one.

12. No Pathogens NIAID & Human Genome 10 50 Excluded pathogens at NIH Health status varies with the facility

13. Norovirus LASP 37 12 th 10 41 DVR Excluded pathogens at NIH Health status varies with the facility

14. Helicobacter 10A 13 th DVR LASP 13th Excluded pathogens at NIH Health status varies with the facility

15. Parvovirus 10A DVR Excluded pathogens at NIH Health status varies with the facility

16. Pinworms & fur mites DVR Excluded pathogens at NIH Health status varies with the facility

17. NorovirusHelicobacterParvovirusPinworms & fur mites No Pathogens NIAID & Human Genome LASP DVR Excluded pathogens at NIH Health status varies with the facility

18. NorovirusHelicobacterNo Pathogens LASP 10A 13 th DVR 10 Parvovirus Excluded pathogens at NIH Health status varies with the facility

19. NorovirusHelicobacterNo Pathogens LASP DVR 37 Parvovirus Excluded pathogens at NIH Health status varies with the facility

20. Excluded pathogens at Frederick Health status varies with the facility NCI Frederick Campus Receiving & Quarantine Norovirus Helicobacter No Pathogens Repository, & Transgenic Mouse Model Laboratory Only 2 are positive Dr. Braden-Weiss can provide Frederick facility status Most are positive

21. Tumor Cell Line Testing Requirements PCR-based testing has replaced MAP-testing to a large extent (MTBM - Molecular testing of Biological Materials) Instructions at LASP AHDL web page All untested cell lines if they have been passaged through rodents outside of the NCI animal program or exposed to rodent serum or if their history is unknown should be submitted Human-derived cells

22. Tissue culture & reagents potentially infected with rodent pathogens Molecular Testing of Biological Materials (MTBM)

23. Taking mice to the Laboratory Special routes and elevators, esp. in CRC Should be rapid and direct Provide food, bedding, fresh water source Practice containment and minimize stress to animals Unless the contrary is approved in the ASP, animals must be euthanized within 12 hours or less

24. Custom Diet Formulations Rodent Feed producers Zeigler, Purina, Harlan, Research Diets Bio-serv Others Must be sterile by gamma-irradiation or autoclavable Consultation with a diet formulation specialist & facility veterinarian is advisable for new test compounds

25. Sentinel Monitoring Program Sentinels Every week, sentinels are exposed to dirty bedding from all cages on rack

26. Sentinel Monitoring Program Sentinels Every 6 weeks, each sentinel cage is tested for a panel of excluded pathogens

27. Sentinel Monitoring Program Sentinels Twice a year, a necropsy with cultures is performed

28. Excluded pathogens Health status varies with the facility

29. Consequences of contamination.. Alteration of experimental measures, tumor growth rates, immunity, etc. Quarantine will limit access to animals Movement of animals ceases Procedure rooms, MIF, etc. may not be used Expensive testing ; expensive extra PPE Cull and slowly repopulate with clean stocks Reduced ability to share mice with colleagues Research progress and productivity may be severely affected

30. SHIPPING MICE ON NIH CAMPUS ON NIH: File out an Internal NIH/IC/ Rodent Transfer request. Must contact receiving facility veterinarian and facility manager to obtain shipping authorization Some facilities may required special testing, others will not accept NCI mice. Most IC’s will accept LASP animals LASP requires all Non-Approved NIH animals to go to R&Q

31. ALL NON-Approved sources MUST go through Receiving and quarantine in Frederick (This includes ANY non-LASP facility at NIH) Fill out on-line importation request https://ncifrederick.cancer.gov/rtp/lasp/intra/ran dq/forms/import_nonapproved.asp https://ncifrederick.cancer.gov/rtp/lasp/intra/ran dq/forms/import_nonapproved.asp Must obtain Complete information from sending facility – including health documents and contact information Contact Sandra Warfield with any questions IMPORTATION OF MICE

32. What to do if your mice test positive for Excluded agents while in Quarantine? Best for LASP facility veterinarians to evaluate health report of sending institution BEFORE mice are shipped. Then you are forewarned of probably Positive results. IMPORTATION OF MICE

33. If Positive – must rederive before you can import into LASP facilities – OR Send to the ACRF 13 th floor or a DVR facility of appropriate health status IMPORTATION OF MICE

34. Very Challenging – Esp. International shipments Every Country is different – US Domestic shipments are relatively uncomplicated Must obtain complete contact and address information from receiving institution facility – EXPORTATION OF MICE

35. Requirement for MTA (Material Transfer Agreement) Set up Accounts with FedEx Express and EXPORTATION OF MICE

36. Contact Jodi Penn or Dr. Melody Roelke- Parker for assistance with all outgoing NIH shipments. Ship only young, healthy animals You are ultimately responsible for the mice selected for shipping. Make sure that the ID and SEX is correct, and that the cages are properly marked EXPORTATION OF MICE START EARLY – CAN TAKE 1 OR MORE MONTHS

37. Questions?