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Cattle are susceptible to experimental infection with the Stetsonville isolate of the transmissible mink encephalopathy (TME) agent. To determine if they are susceptible to other TME isolates, two groups of calves were inoculated intracerebrally with homogenate of mink brain containing the Hayward isolate or the Blackfoot isolate. For comparison, a third group was inoculated with a brain homogenate from a steer infected with the Stetsonville isolate in its primary cattle passage and a fourth group was inoculated with a pool of brain homogenate from three cattle experimentally infected with a sheep and goat scrapie agent in its primary cattle passage. Clinical signs of neurological disease appeared in each steer of every group between 15 and 25 months after inoculation. An encephalopathy characterized by severe spongiform change and pronounced astrocytosis occurred in the three groups inoculated with the TME agent. In contrast, the neurohistological changes in the steers inoculated with the cattle-passaged scrapie agent were slight and subtle. Analysis of the octapeptide repeat region of the bovine protease-resistant protein (PrP) gene showed that variations in incubation period, clinical signs, and neurohistological changes were unrelated to the homozygous or heterozygous condition of six or six/five octapeptide repeats.

To determine whether the aetiological agent of bovine spongiform encephalopathy (BSE) is pathogenic for mink, standard dark mink were inoculated with coded homogenates of bovine brain from the U.K. Two homogenates were from cows affected with BSE. The third was from a cow that came from a farm with no history of having had BSE or having been fed ruminant-derived, rendered by-products, the proposed vehicle for introduction of the BSE agent. Each homogenate was inoculated intracerebrally into separate groups of mink and a pool of the three was fed to a fourth group. Signs of neurological disease appeared in mink an average of 12 months after intracerebral inoculation and 15 months after feeding. Decreased appetite, lethargy and mild to moderate pelvic limb ataxia were the predominant clinical signs, quite unlike the classic clinical picture of transmissible mink encephalopathy (TME). Microscopic changes in brain sections of most affected mink were those of a scrapie-like spongiform encephalopathy. Vacuolar change in grey matter neuropil was accompanied by prominent astrocytosis. Varying greatly in severity from one mink to another, the degenerative changes occurred in the cerebral cortex, dorsolateral gyri of the frontal lobe, corpus striatum, diencephalon and brainstem. Although resembling TME, the encephalopathy was distinguishable from it by less extensive changes in the cerebral cortex, by more severe changes in the caudal brainstem and by sparing of the hippocampus. The results of this study extend the experimental host range of the BSE agent and demonstrate for the first time the experimental oral infection of mink with a transmissible spongiform encephalopathy agent from a naturally infected ruminant species.

The distribution of the enzyme tyrosine aminotransferase in tissues of mink, Mustela vison, was investigated. High levels of enzymatic activity were detected only in liver, documenting the hepatic-specific nature of this enzyme in this species. Further studies disclosed that tyrosine aminotransferase is not absent from non-hepatic tissues because of the lack of the use of a stabilized buffer, sensitivity to temperature, or due to the presence of an inhibitor. Collectively, these results suggest that the enzymatic assay of tyrosine aminotransferase will be unlikely to be an efficacious approach for identifying mink that are heterozygous for the autosomal recessive deficiency of this enzyme that is common in dark mink.

This chapter describes some observations on the occurrence of canine distemper (CD) on mink farms and experimental trials using mink and ferrets. Ferrets—because of their high susceptibility to canine distemper virus (CDV)—show an invariably fatal course, which makes them the most satisfactory animal for conducting many distemper experiments. Vaccination is the only suitable means for the control of mink and ferret distemper. Attenuated live CDV vaccines produce a more dependable, longer lasting immunity and have replaced inactivated vaccines for ranch-raised mink and pet ferrets. Present-day distemper vaccines for mink are inexpensive and effectively immunize susceptible mink, and they can be combined with other vaccines to protect against mink virus enteritis, botulism, and Pseudomonas infections. In the case of dogs, foxes, mink, and ferrets and perhaps all other Mustelidae, Canidae, and Procyonidae, maternal antibody is a double-edged sword protecting young animals from distemper and conversely blocking early chicken embryo propagated (CEP) vaccination.

Mink with Aleutian disease developed severe anemia within a few months after infection. Evaluation of erythropoiesis and erythrocyte survival demonstrated that the anemia was caused by increased erythrocyte destruction, complicated in some cases by decreased or inadequate erythropoiesis. An inverse relationship existed between the amount of IgG on affected mink erythrocytes and the erythrocyte half-life. However, the number of IgG molecules/erythrocyte were not high enough to be detected by direct Coombs' test, with the exception of one case. Inadequate erythropoiesis was reflected by lower plasma iron turnover levels and reticulocyte numbers than expected considering the severity of the anemia involved.

Hypergammaglobulinemia (Aleutian disease or AD) of mink has been produced by the inoculation of afifected tissue suspensions and cell-free filtrates (Henson et al, 1962b, 1963a; Karstad and Pridem, 1962; Russell et al, 1962; Trautwein et al, 1962; P. G. White, personal communication). The filterable substance is particulate, since it can nearly all be removed from aqueous suspension by centrifugation at 95,000 rcf for 1 hour (Henson et al, 1963a). The causal agent (which we will provisionally call a virus) in the form of a crudely ground tissue suspension is resistant to 0.3(^) formalin for 2 weeks, but not for 40 weeks, at 5 C (Henson et al, 1962b). The present paper confirms the demonstration of the virus in the urine (Kenyon et al, 1963) and forms part of an investigation of the natural history of the disease among mink.

The occurrence of abnormal bodies in the cytoplasm of neutrophils, eosinophils, monocytes and lymphocytes of Aleutian (aa) mink is reported. Similarities of these bodies to the leukocyte abnormalities of Chediák-Higashi syndrome of children are pointed out.

Hypergammaglobulinemia in mink was produced by the injection of crude tissue suspensions from mink with spontaneous Aleutian disease. The initiating factor was found to be resistant to 0.3 per cent formalin for 2 weeks but not 40 weeks at 5°C. Foreign antigens as well as formalinized normal mink tissue from homologous and heterologous genotypes did not cause a detectable change in the serum protein values. Mink homozygous recessive for the Aleutian gene were found to be significantly more susceptible to the experimental disease. Possible pathogenetic mechanisms as well as similarities between the mink disease and certain immunologic and connective tissue diseases of man are discussed.

The Wisconsin FXNO strain of attenuated live-virus egg-propagated distemper vaccine apparently did not cross the placental barrier when given to pregnant mink and ferrets. No deleterious effect was observed on the mink or ferret foetuses.

1. Clinical pathologic studies were performed on mink affected with a progressive form of muscular dystrophy. Serum levels of muscle enzymes, including creatine phosphokinase, aldolase, and glutamic oxalacetic transaminase, of affected mink were markedly elevated. A significantly increased urinary creatine/creatinine ratio was a consistent finding in the affected mink, and this ratio was usually greater than two for affected mink as compared to a ratio of less than one for nonaffected mink. 2. Marked elevation of muscle enzymes in serum and an increase in the urinary creatine/creatinine excretion ratio are consistent clinical pathologic findings in human amyotonic forms of muscular dystrophy. On the basis of these clinical alterations, the muscular dystrophy of mink appears similar to the amyotonic forms of human muscular dystrophy.

Gross and microscopic lesions of Aleutian disease (AD) in mink and hypergammaglobulinemia in ferrets were compared. Both conditions were characterized by widespread proliferation of plasma cells, but proliferation was more prominent in mink infected with AD. Arteritis did not occur in hypergammaglobulinemic ferrets. Minimal or no glomerular alterations occurred in infected ferrets, but were severe in mink infected with AD. Bile duct proliferation was more prominent in diseased mink. Tissue alterations suggested that AD in Aleutian genotype mink is more rapidly progressive than is AD in ferrets, causing overt clinical disease and death. In contrast, hypergammaglobulinemia in ferrets appeared to progress more slowly, with little clinical evidence of disease. This is probably the result of a paucity of glomerular lesions in ferrets. Possible mechanisms to explain the differences in the development of lesions are discussed.

Transmissible mink encephalopathy (TME) virus retained biological activity after prolonged storage in formalin (about three and a half years) and in paraffin tissue blocks used for histologic preparations (about six and a half years). Thus, TME tissues in formalin and in paraffin blocks should be handled as contaminated materials.

A prolonged mean template bleeding time of 13 minutes was present in nine Aleutian mink affected with Chediak-Higashi syndrome (CHS) compared with 4 minutes in dark control mink. The concentrations of blood platelets in normal and affected animals did not differ significantly. However, in mink with CHS, a marked disturbance of platelet response to collagen was present. Administration of aspirin and indomethacin completely blocked CH platelet response to collagen. Blood platelet adenosine triphosphate and adenosine diphosphate values from mink with CHS were significantly less than those of normal mink, and the platelet adenosine triphosphate/adenosine diphosphate ratios were 10.31 in affected mink and 2.74 in normal mink. These findings are consistent with our previous investigations in affectd cattle and persons and indicate that a "storage pool disease" of platelets exist in the mink with CHS.

Hcmatologic atad patltologic examination on thirty-live mink, clinically affectedwith gray diarrhea, were carried otut. Four had other recognizable diseases. Twenty-two1?ad microscopic stomach lesions, not described in other mink diseases. The lesions weremultifocal ancl consisted of loss of the ntiddle and basal layers c>f the mucosa, with neutro-phil and monont?c1ear cell infiltratiort. Fibrosis was observecl in the stomach lesions ofsome. Dircct ancl indirect fluorescent antibody tecltniques, tttilizing sera from affectedmink, failed to demonstrate an aul-oantibocly in them. Hematologic responses of aflecteclmink varied widely.

Three antigenic forms of natural field isolates of mink enteritis virus were revealed with a panel of monoclonal antibodies generated against the closely studied feline panleukopenia virus and canine parvovirus-2 virus. Two types (types 2 and 3) were shown to be closely related by agar-gel precipitin tests and by restriction enzyme mapping. However, types 2 and 3 differed from the type 1 isolates in the same tests. In cross-protection studies, inactivated viral vaccines made from any one of the 3 variant types of mink enteritis virus protected mink against challenge exposure by the homologous, as well as the heterologous, antigenic types.

Affinity chromatography on immobilized equine complement Clq was used for the isolation of complement-binding immune complexes in sera of mink infected with Aleutian disease virus. Immune complexes were isolated and quantitated from 4 of 5 infected mink, as early as 2 weeks after infection and before hypergammaglobulinemia had appeared. The quantity of immunoglobulin G in these immune complexes ranged from 180 to 370 micrograms/ml serum. There were no Clq-binding immune complexes found in mink which were negative for Aleutian disease antibody. Using 125I-labeled BSA-anti-BSA complexes, we demonstrated that the affinity columns bound selectively immune complexes which had formed in antibody excess, whereas immune complexes in antigen excess were not bound. By neutralization of sensitized virus with anti-mink IgG serum, non Clq-binding immune complexes were also detected, which indicates that circulating immune complexes in persistently infected mink are heterogeneous as far as their reactivity with equine Clq is concerned.

Fulminating pneumonia was produced in mink by the intratracheal administration of Pseudomonas aeruginosa. The sequence of pulmonary lesions was focal inflammation, focal necrosis, and widespread inflammation and necrosis. Secondary lesions of peracute hemorrhage and necrosis were the result of bacterial spread via the airways. Invasion of vessel walls by P aeruginosa was a terminal event and was secondary to bacillary invasion and necrosis of adjacent tissues. Regional (lymphatic) and systemic spread of bacteria followed the development of pulmonary lesions, but there was little morphologic evidence of tissue damage in other organs. Immunofluorescence studies showed that P aeruginosa antigen was dispersed within pulmonary cells and was free in the lung parenchyma. Mink surviving beyond postinfection hour 60 had a macrophage infiltration into limited pulmonary lesions. A vaccine trial was conducted with P aeruginosa lipopolysaccharides (LPS) used as antigen, and an enzyme-linked immunosorbent assay was used to detect antibody. Antibody was detected in mink after vaccination with LPS or natural exposure. Mink with antibody to LPS, from vaccination or naturally acquired, were resistant to experimental infection.

Twenty-five mink were inoculated with mink enteritis virus (MEV). Fecal specimens were collected daily and were simultaneously evaluated for MEV antigen by use of a direct enzyme-linked immunosorbent assay (ELISA), hemagglutination (HA), and electron microscopy. Results of the evaluations indicated that MEV was shed in the feces on postinoculation days 5 and 6. The virus was not detectable by ELISA or HA after postinoculation day 6, although viruses were found in reduced numbers by use of electron microscopy. The ELISA was specific for MEV, and the sensitivity of the ELISA for MEV was comparable with that of HA.

A central nervous system disease of mink occurred in three unrelated fur farms in Oregon in September, 1981. Only kits four to five months old were affected. Clinical signs consisted of posterior ataxia progressing to complete posterior paralysis with loss of motor control and sensation. Complete or partial recovery occurred in approximately 1.5 months in most mink. Microscopic lesions consisted of severe nonsuppurative meningoencephalitis and meningomyelitis with vacuolation of the white matter of the brain and spinal cord. Canine distemper virus infection and other recognized causes were ruled out on the basis of clinical signs, history, lesions, or laboratory findings. Experimental inoculations of mink with brain and spinal cord specimens from affected mink failed to reproduce the disease.

An outbreak of tularemia in farm raised mink is reported. Twenty-six of approximately 5000 mink succumbed within a 10 day period. Prodromal signs were minimal. Necropsy revealed necrotic nodules scattered in the parenchyma of the lungs, liver, spleen, and mesenteric lymph nodes. Francisella tularensis was isolated from spleens, livers and lungs.

Parvoviruses from mink (mink enteritis virus [MEV]), cats (feline panleukopenia virus [FPV]), raccoons (raccoon parvovirus [RPV]), and dogs (canine parvovirus [CPV]) were compared. Restriction enzyme analysis of the viral replicative-form DNA revealed no consistent differences between FPV and RPV isolates, but CPV and MEV isolates could be distinguished readily from other virus types. Feline panleukopenia virus, RPV, and MEV, but not CPV, replicated to high titers in mink. However, on the first passage, disease and microscopic lesions were observed only in mink inoculated with MEV. Feline panleukopenia virus and RPV isolates replicated in ferrets, but disease or microscopic lesions were not observed. Feline panleukopenia virus and RPV isolates could be passaged repeatedly in mink and ferrets. Virulence of FPV and RPV isolates was low compared with that of MEV, and only a single mink inoculated with FPV or with RPV developed clinical disease on the sixth passage of virus.

Epizootics of pneumonia in mink caused by Pseudomonas aeruginosa were investigated to characterize the serotype of organisms and to identify possible predisposing factors. Most epizootics were associated with P aeruginosa Fisher serotype 1, and a few were associated with 3 other serotypes. There were no predisposing factors identified that could be used to differentiate farms affected and those not affected with pseudomonas pneumonia. Cultural studies indicated that P aeruginosa was present in mink from affected and nonaffected herds. Organisms isolated included serotypes associated with naturally occurring disease. Serostudy results were similar among herds. A prospective field vaccination trial did not yield definitive results, since only slight losses occurred in both vaccinated and nonvaccinated mink. Significant levels of antibody were detected in mink 15 to 17 weeks after they were given a single dose of P aeruginosa lipopolysaccharide vaccine.

Normal and Aleutian disease affected mink from ranches with a high prevalence of Aleutian disease were killed at approximately monthly intervals from July to November. Serum was subjected to zone electrophoresis and the serum protein changes were compared to the histologic stage of development of the renal, hepatic, and arterial changes. The initial renal lesions were interstitial infiltrations of plasma cells and lymphocytes with later development of glomerular changes. The arterial lesions were early medial necrosis followed by the appearance of fibrinoid and later by healing with concentric fibrillar proliferation. There seemed to be a direct relation between the severity of renal, hepatic, and arterial changes and the magnitude of hypergammaglobulinemia. Possible pathogenetic mechanisms are discussed.

The method of probit analysis was applied to the estimation of chicken embryo-propagated distemper virus infectivity.

Observations showed that the mosquito,Aedes fitchii (Felt andYoung), readily feeds on mink. Injection of homogenized mosquitoes, held for various periods after an infectious blood meal, into susceptible mink revealed that this mosquito retained Aleutian disease (AD) virus for 35 days. The virus in groundA. fitchii was titrated immediately and 15 days after infective feeding. The titer decreased from 104ID50/ml to 102ID50/ml during this time. Conversely, AD virus did not persist for six days inAedes aegypti (Linnaeus). Homogenized pools of heads combined with salivary glands ofA. fitchii 5, 10, and 15 days after infective feeding were injected into susceptible mink, viral infectivity was demonstrated in this region at 10 and 15 days after infective feeding but not at 5 days. This study suggests that replication of AD virus may occur inA. fitchii and a true vectorpathogen relationship exists between AD virus and certain arthropods.