Health Evaluation of Experimental Laboratory Mice

Tanya Burkholder1, Charmaine Foltz1, Eleanor Karlsson1, C. Garry Linton1, Joanne M. Smith1

1 Division of Veterinary Resources, Office of Research Services, National Institutes of Health, Bethesda, Maryland
Publication Name:  Current Protocols in Mouse Biology
Unit Number:   
DOI:  10.1002/9780470942390.mo110217
Online Posting Date:  June, 2012
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Abstract

Good science and good animal care go hand in hand. A sick or distressed animal does not produce the reliable results that a healthy and unstressed animal produces. This unit describes the essentials of assessing mouse health, colony health surveillance, common conditions, and determination of appropriate endpoints. Understanding the health and well‐being of the mice used in research enables the investigator to optimize research results and animal care. Curr. Protoc. Mouse Biol. 2:145‐165 © 2012 by John Wiley & Sons, Inc.

Keywords: mouse; health; evaluation; disease; body condition; end‐point; surveillance

     
 
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Table of Contents

  • Introduction
  • Colony Health Surveillance
  • Examination and Assessment of the Mouse
  • Common Clinical Health Conditions of Mice
  • Defining and Refining Endpoints
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

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Figures

  •   FigureFigure 1. Facial expressions in mice indicating pain and/or distress include squinted eyes, contracted skin around nose, and ears pulled back.
  •   FigureFigure 2. Body Condition Scoring (BCS) is a quick, easy and reliable method for assessing mouse health. It utilizes a scoring system of 1 to 5 with 3 being the optimal condition, 1 being emaciated, and 5 being obese.
  •   FigureFigure 3. Fight wounds. (A) Typical pattern of miliary wounds on the side of the body. (B) Deep wound on the caudal portion of the rump. (C) Wounds and associated swelling on the tail.
  •   FigureFigure 4. Ear dermatitis. Crusty lesions on and below the ear associated with loss of an eartag.
  •   FigureFigure 5. Barbering. (A) Thin coat with short stubby hairs on the head and neck. (B) Two mice, one with minor barbering and one with extensively barbered fur. Note that the skin is healthy in these cases.
  •   FigureFigure 6. Ulcerative dermatitis: deep ulcerative lesion with redness and moist surface at the base of the neck.
  •   FigureFigure 7. Ringtail. Circular constriction is noted with normal skin coloration. There may be one ring as shown, or a series of rings around the tail.
  •   FigureFigure 8. Tumor. A subcutaneous irregular mass is shown caudal to the front leg of this nude mouse.
  •   FigureFigure 9. Conjunctivitis. The left eye demonstrates swelling of the eyelids, redness of conjunctiva, and serous discharge. Compare to the normal right eye.
  •   FigureFigure 10. Keratitis. The left cornea is white, opaque, and dry. Compare to the normal right eye.
  •   FigureFigure 11. Retrobulbar abscess. Swelling and discoloration are noted below and caudal to the orbit of the left eye. Compare to the normal right eye.
  •   FigureFigure 12. Arthritis. The mouse on the left has swelling of the hock (ankle) joint associated with arthritis. A normal mouse is shown on the right.
  •   FigureFigure 13. Malocclusion. The incisor teeth are unequal in length and the shorter tooth angles inward more than normal. Teeth may be observed to grow inward or outward, and may be very curved or broken as shown.
  •   FigureFigure 14. Runts. A runt or small mouse is shown on the left compared with its normal littermate on the right.
  •   FigureFigure 15. Imperforate vagina. Both are female mice. The mouse on the left lacks the normal vaginal opening and shows subcutaneous perineal swelling due to accumulated secretions which are unable to drain. Normal mouse is shown on the right.
  •   FigureFigure 16. Bulbourethral gland cyst. Swelling in the right side of the scrotum is caused by a cystic bulbourethral gland. This can be confirmed by performing a needle aspiration, with fluid indicating a cyst while no fluid may be indicative of a tumor.
  •   FigureFigure 17. Ascites. Fluid accumulation within the abdomen leads to a potbellied appearance with prominent spine.
  •   FigureFigure 18. Rectal prolapse. Red, edematous mucosal tissue is seen bulging from the rectal orifice.

Videos

Literature Cited

   Clark, M.D., Krugner‐Higby, L., Smith, L.J., Heath, T.D, Clark, K.L., and Olson, D. 2004. Evaluation of liposome‐encapsulated oxymorphone hydrochloride in mice after splenectomy. Comp. Med. 54:558‐563.
   Flecknell, P. 2002. Replacement, reduction and refinement. ALTEX 19:73‐78.
   Foltz, C.J. and Ullman‐Cullere, M. 1999. Guidelines for assessing the health and condition of mice. Lab. Anim. 28:28‐32.
   Fox, J.G., Anderson, L.C., Loew, F.M., and Quimby, F.W. 2002. Laboratory Animal Medicine, 2nd ed. Academic Press, San Diego.
   Hedrich, H.J., Bullock, G., and Petrusz, P. 2004. The Laboratory Mouse. Elsevier Academic Press, San Diego.
   Hendriksen, C.F.M. and Steen, B. 2000. Refinement of vaccine potency testing with the use of humane endpoints. ILAR J. 41:105‐113.
   Hess, S.E., Rohr, S., Dufour, B.D., Gaskill, B.N., Pajor, E.A., and Garner, J.P. 2008. Home improvement: C57BL/6J mice given more naturalistic nesting materials build better nests. J. Am. Assoc. Lab. Anim. Sci. 47:25‐31.
   Langford, D.J., Bailey, A.L., Chanda, M.L., Clarke, S.E., Drummond, T.E., Echols, S., Glick, S., Ingrao, J., Klassen‐Ross, T., LaCroix‐Fralish, M.L., Matsumiya, L., Sorge, R.E., Sotocinal, S.G., Tabaka, J.M., Wong, D., van den Maagdenbert, A.M., Ferrari, M.D., Craig, K.D., and Mogil, J.S. 2010. Coding of facial expressions of pain the laboratory mouse. Nat. Methods 7:447‐450.
   Lawson, G.W., Sato, A., Fairbanks, L.A., and Lawson, P.T. 2005. Vitamin E as a treatment for ulcerative dermatitis in C57BL/6 mice and strains with a C57BL/6 background. Cont. Top. 44:18‐21.
   Minecci, P.C., Deans, K.J., Hansen, B., Parent, C., Romines, C., Gonzales, D.A., Ying, S., Munson, P., Suffredini, A.F., Feng, J., Solomon, M.A., Banks, S.M., Kern, S.J., Danner, R.L., Eichacker, P.Q., Natanson, C., and Solomon, S.B. 2007. A canine model of septic shock: Balancing animal welfare and scientific relevance. Am. J. Physiol. Heart Circ. Physiol. 293:H2487‐H2500.
   Montgomery, C.A. 1990. Oncological and toxicological research: Alleviation and control of pain and distress in laboratory animals. Cancer Bull. 42:230‐237.
   Morton, D.B. 2000. A systematic approach for establishing humane endpoints. ILAR J. 41:80‐86.
   Morton, D.B. and Griffiths, P.H. 1985. Guidelines on the recognition of pain, distress and discomfort in experimental animals and an hypothesis for assessment. Vet. Rec. 116:431‐436.
   National Research Council. 2011. The Guide for the Care and Use of Laboratory Animals, 8th ed. National Academies Press, Washington, D.C. (available at http://grants.nih.gov/grants/olaw/Guide‐for‐the‐Care‐and‐Use‐of‐Laboratory‐Animals.pdf).
   Olfert, E.D. and Godson, D.L. 2000. Humane endpoints for infectious disease animal models. ILAR J. 41:99‐104.
   Paster, E.V., Villines, K.A., and Hickman, D.L. 2009. Endpoints for mouse abdominal tumor models: Refinement of current criteria. Comp. Med. 59:234‐241.
   Percy, D.H. and Barthold, S.W. 2007. Pathology of Laboratory Rodents and Rabbits, 3rd ed. Blackwell Publishing, Ames, Iowa.
   Pritchett‐Corning, K.R., Girod, A., Avellaneda, G., Fritz, P.E., Chou, S., and Brown, M.J. 2010. Handbook of Clinical Signs in Rodents and Rabbits. Charles River Laboratories, Wilmington, Mass.
   Roughan, J.W., Wright‐Williams, S.L., and Flecknell, P.A. 2009. Automated analysis of postoperative behavior: Assessment of HomeCageScan as a novel method to rapidly identify pain and analgesic effects in mice. Lab. Anim. 43:17‐26.
   Russell, W.M.S. and Burch, R.L. 1959. The Principles of Humane Experimental Technique. Methuen and Co., London.
   Sass, N. 2000. Humane endpoints and acute toxicity testing. ILAR J. 41:114‐123.
   Stokes, W.S. 2000. Reducing unrelieved pain and distress in laboratory animals using humane endpoints. ILAR J. 41:59‐61.
   Stokes, W.S. 2002. Humane endpoints for laboratory animals used in regulatory testing. ILAR J. 43:S31‐S38.
   Toth, L.A. 1997. The moribund state as an experimental endpoint. Contemp. Top. Lab. Anim. Sci. 36:44‐48.
   Toth, L.A. 2000. Defining the moribund condition as an experimental endpoint for animal research. ILAR J. 41:72‐79.
   Toth, L.A., and Gardiner, T.W. 2000. Food and water restriction protocols: Physiological and behavioral considerations. Contemp. Top. Anim. Sci. 39:9‐17.
   Ullman‐Cullere, M. and Foltz, C.J. 1999. Body condition scoring: A rapid and accurate method for assessing health status in mice. Lab. Anim. Sci. 49:319‐323.
   Wallace, J. 2000. Humane endpoints and cancer research. ILAR J. 41:87‐93.
   Williams‐Fritze, M.J., Carlson‐Scholtz, J.A., Zeiss, C., Deng, Y., Wilson, S.R., Franklin, R., and Smith, P.C. 2011. Maropitant citrate for treatment of ulcerative dermatitis in mice with a C57BL/6 background. J. Am. Assoc. Lab. Anim. Sci. 50:221‐226.
Key References
   Hedrich et al., 2004. See above
  This book contains excellent introductory information in the first few chapters, with strain characteristics in Chapter 3. Detailed systems information; excellent as a reference.
   Percy and Barthold, 2007. See above.
  The first chapter of this book contains excellent general pathology information on laboratory mice, including strain characteristics.
   Pritchett‐Corning et al., 2010.
  This is a pictorial guidebook aimed at animal care personnel, organized by anatomic and organ system sections, which has additional information on rodent clinical observations.
Internet Resources
  http://phenome.jax.org
  Mouse phenome database maintained by The Jackson Laboratory with detailed phenotype strain survey data. The Jackson Laboratory site http://www.jax.org has links to many valuable resources such as mouse nomenclature, resource manuals, and specific strain information.
  http://www.ors.od.nih.gov/sr/dvr/od/Documents/Post_Op_Form.docx
  A link to a post‐op monitoring form that may be useful to the investigative team and/or the veterinary team.
  http://www.criver.com/en‐US/ProdServ/ByType/ResAnimalDiag/Pages/home2.aspx
  An example of commercial laboratory services for health surveillance.
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