                                   
                                   
                Common Lesions and Incidental Findings
                         in Laboratory Rodents
                                   
                     Charles B. Clifford, DVM, PhD
                       Senior Staff Pathologist
                      Charles River Laboratories
                                    
  Introduction
  
  Pathologists are trained, intentionally and appropriately, to think of a complete list of
  differentials when faced with any given lesion.  As training advances we are admonished
  to, "when you hear hoofbeats, think horses, not zebras".  In real life, however, many
  lesions in modern laboratory rodents, i. e., the real "horses", are not included in the
  "classical" lists of differential diagnoses.  Although each lesion surely has a specific cause,
  whether a metabolic derangement or a microbe, and although our job is to determined that
  cause, the morphologic appearance of the lesion is often non-specific.  To further
  complicate matters, many lesions do not indicate the presence of a threat to the health of
  an individual animal, a colony of animals, or to the research in which they are used or
  intended. 
  
  This discussion will cover a few of the lesions commonly encountered in diagnostic and
  routine health monitoring of laboratory rodents.  Although some of these lesions can have
  individual health consequences, and can even be confounding factors in some studies, they
  are generally included under the broad category of incidental lesions.  Many are significant
  only in that they must be distinguished from diseases on the traditional list of differential
  diagnoses. 
  
  
  Mice
  
     Skin Lesions
  
     Bite Wounds and Claw Marks
   The most common skin lesion observed in mice housed or shipped in groups.  Can
     appear as "epidemics" if mice are re-arranged, or stressed.  Can be complicated by
     bacterial infection.  Mostly on dorsum and tail.
     Follicular cysts in glabrous animals, immunodeficient and immunocompetent..
   Nude and hairless mice develop cutaneous cysts, representing follicles distended with
     distorted hair shafts and keratinaceous debris.  These may predispose to cutaneous
          abscesses subsequent to cyst colonization with opportunistic bacteria. 
     Barbering
   Hair loss, often in patterns, usually without damage to skin.  Usually affects multiple
     animals in a group.  Mechanical hair loss may also be caused by some feeder designs. 
     Dams may also chew whiskers or ears off pups.
     Streptococcosis
   Can cause cutaneous abscesses, pododermatitis, tail lesions.  Can be systemic, with
     abscesses in heart, kidney, lung, etc.  The systemic form is most frequently observed in
     animals soon after weaning, C3H and DBA mice seem affected most often, but no
     strain predilections have been documented in the literature.  
     Preputial/Clitoral Gland Abscesses
   Variety of opportunistic bacteria common in environment are involved,
     Staphylococcus, Proteus, Pseudomonas, Pasteurella pneumotropica, E. coli, etc. 
     Factors governing lesion development may related to bacterial concentration in
     bedding, and possibly to stress.
     Ringtail
   Cause not clear.  Literature claims humidity/temperature.  Affects neonates.  
  
     Ocular Lesions
  
     Retinal Degeneration (light )
   Well described in literature.  Especially in albino strains/stocks.  Primarily important to
     distinguish from genetic retinal degeneration, such as rd gene. 
     Congenital and/or Genetic Eye Lesions (Retinal Dysplasia, Microphthalmia, Ectopic
       pupil)  Vary with strain, retinal degeneration affects almost 100% of some strains.  
  
     Internal Lesions
  
     Multifocal mineralization: heart, tongue, diaphragm
   Pale raised foci on the tongue, "frosted" appearance to the epicardium.  Can also be
     within myocardium.  Seen in DBA/2, BALB/c, occasionally in other mice.  The
     pathogenesis of the lesion is unclear.  No clinical effects.
     Splenic melanosis (C57BL6 mice)
   Not a lesion.  Should not be confused with hemosiderosis or necrosis.
     Cardiomyopathy (C3H mice)
   Published once.  Common in at least several lines of C3H.  Can be fatal, especially in
     female breeders.
     Amyloidosis
   A leading cause of death in CD-1 mice.  In order of likelihood to be affected: kidney,
     small intestine, mesenteric lymph nodes, gonads, liver, thymus, adrenals, salivary
     glands, spleen, heart.  Cause and type (primary or secondary) not clear.
     Alveolar Histiocytosis
   Multifocal, usually sub-pleural, accumulations of foamy alveolar macrophages.  Can be
     accompanied by some intersitial thickening and a few lymphocytes.  Number and size
     of these accumulations increases with age.
   Eosinophilic Crystalline Pneumonia
   Accumulation of macrophages and granulocytes, with intracellular and extracellular
     eosinophilic, refractile, isotropic, elongate crystals.  Most likely from
     bronchial/bronchiolar secretory product.
     "Idiopathic" Hepatic Necrosis in NIH Black mice
   One abstract.  Nearly 100% incidence of perivascular necrotic foci.  Not transmissible.
     Present in germ-free and SPF animals.
  
  Rats
  
     Skin Lesions (in addition to those in mice)
  
     Staphylococcosis
   Affects rats and other species, but rats seem most commonly affected.  Can infect
     wounds, including minor wounds.  Can appear as moist, ulcerative enlarging lesion
     behind the ear, and extending down the neck.
     Auricular Chondropathy
  
     Ocular Lesions
  
     Corneal Dystrophy
   Extremely high incidence in F-344 rats, although the incidence varies with sub-line. 
     Can be associated with mild leukocytic infiltrate, but should not be mistaken for post-
     inflammatory scarring.  If extensive, can obstruct ophthalmoscopic examination.  May
     increase in severity with age.
     Porphyria
   The most common cause is mild dehydration during shipping.  Can be observed after a
     number of non-infectious stresses, including elevated temperature.  Can also be caused
     be a variety of infectious disease including mycoplasmosis and sialodacryoadenitis,
     although this occurs less frequently.
  
     Internal Lesions
  
     Pulmonary Granulomas in BN rats
   Not published.  25% incidence at 8 weeks of age of multifocal granulomatous
     pneumonia, with bronchiolar infiltration of eosinophils.
     Cardiomyopathy
     Progressive Renal Disease
     Hydronephrosis
   May be unilateral or bilateral, right kidney affected more often, males more often. 
     Probably multigenic in some rats (Sprague-Dawley), single gene inheritance in others
     (Gunn rat).
     Pyelonephritis
   Can be due to any of a variety of Gram negative or Gram positive bacteria.  Most
     often occurs in females, especially breeders.  Lewis rats may have a higher incidence.
   White spots in the liver
   Presumed to be bacterial in origin, although cultures are generally negative. 
     Histologically, these are most frequently characterized by accumulations less than 1
     mm in diameter of mononuclear cells, with occasionally some neutrophils and a few
     centrally located degenerate hepatocytes.  The lack of degenerate heatocytes at the
     periphery of the lesions, and the mild neutrophil infiltration suggests that the lesions
     are in a stage of regression.  When cultures are positive, a variety of opportunistic
     bacteria may be found, as well as some bacteria often considered to be non-
     pathogenic.  This suggests that these may be due to enteric organisms gaining access
     to the portal circulation, then being rapidly phagocytoses and killed in the liver.  The
     activation of Kupffer cells might release sufficient cytokines to results in a small local
     accumulation of leukocytes.  Some evidence suggests that there may be a slightly
     higher incidence soon after weaning.
  
  
  Guinea Pigs
  
     Skin Lesions ( in addition to those above)
  
     Age-related alopecia
   Commonly observed in older animals, especially boars.  Hair becomes sparse,
     especially on flanks and on the back.  This can also be seen in pregnant females,
     especially older ones.  Similar changes are also observed in aged rats.
     Pododermatitis
   Common in older animals housed on wire.  Ulcerated lesions on the weight bearing
     surface of the feet.
     Scrotal Plugs
   Common in older males.  Not truly a lesion.
  
     Internal Lesions
  
     Segmental Nephrosclerosis
   Extremely common in older guinea pigs.  Unknown cause.  Distinguish from
     interstitial nephritis due to E. cuniculi by degree of fibrosis and virtual lack of
     leukocytic infiltration in segmental nephrosclerosis.
     Idiopathic Hepatic Necrosis
   Cause unknown.  Most often subcapsular, may be extensive.  Appearance is consistent
     with a hypoxic or ischemic cause.  Older lesions may have some central mineralization
     and proliferation of cells at the periphery.
     Multifocal Mineralization
   May be spontaneous. May possibly be increased in Hypovitaminosis C.
     Pulmonary Foreign-Body (plant) Granulomas
   The most common grossly visible lung lesions in VAF  guinea pig lungs.
     Osseous metaplasia in lung
   Occurs sporadically in guinea pigs and other species.
  
                              References
                                    
  Faccini, J.M., Abbott, D.P., and Paulus, 1990, D.P.P., Mouse Histopathology, Elsevier,
  Amsterdam.
  
  Fox, J.G., Cohen, B.J., and Loew,F.M., 1984, Laboratory Animal Medicine, Academic
  Press, Inc., San Diego.
  
  Boorman, G.A., Eustis, S.L., Elwell, M.R., Montgomery,C.A., and MacKenzie, W.F.,
  1990, Pathology of the Fischer Rat, Academic Press, Inc., San Diego.
  
  Mohr,U., Dungworth, D.L., Capen, C.C., 1994, Pathobiology of the Aging Rat, Vols 1
  and 2, ILSI Press, Washington, D.C.
  
  Percy, D.H., and Barthold, S.W., 1993, Pathology of Laboratory Rodents and Rabbits,
  Iowa State University Press, Ames.