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A severe hyperlipemia in mink, with a pattern that suggested recessive inheritance, was observed at a farm in Norway. On a normal mink diet, affected animals had grossly elevated levels of plasma triglycerides which decreased towards normal on a low-fat diet. Normal minks had the main part of their plasma cholesterol in the HDL fraction. Affected minks, although severely hypertriglyceridaemic, had almost normal levels of both LDL and HDL. Affected minks frequently had lipogranulomas in the mesentery and the pancreas. The lipogranulomatous tissue contained spaces filled with an amorphous, sudanophilic substance with many foamy macrophages in the fibrous tissue between the lesions. Separation of postheparin plasma on heparin-agarose revealed that the affected minks had no detectable lipoprotein lipase activity but normal activity of hepatic lipase. Both normal and affected minks had inactive lipoprotein lipase protein in pre- and post-heparin plasma. This protein, which eluted before the active lipase from heparin-agarose, probably corresponds to lipase monomers. The presence of lipoprotein lipase mass in the affected minks, but no activity, indicates that there might be a point mutation in the lipase gene. The minks provide a new animal model for studies on pancreatitis induced by hypertriglyceridemia and on lipoprotein metabolism in the lipoprotein lipase-deficient state and show features similar to those found in human hyperlipoproteinemia type I.

A severe hyperlipemia in mink, with a pattern that suggested recessive inheritance, was observed at a farm in Norway. On a normal mink diet, affected animals had grossly elevated levels of plasma triglycerides which decreased towards normal on a low-fat diet. Normal minks had the main part of their plasma cholesterol in the HDL fraction. Affected minks, although severely hypertriglyceridaemic, had almost normal levels of both LDL and HDL. Affected minks frequently had lipogranulomas in the mesentery and the pancreas. The lipogranulomatous tissue contained spaces filled with an amorphous, sudanophilic substance with many foamy macrophages in the fibrous tissue between the lesions. Separation of postheparin plasma on heparin-agarose revealed that the affected minks had no detectable lipoprotein lipase activity but normal activity of hepatic lipase. Both normal and affected minks had inactive lipoprotein lipase protein in pre- and post-heparin plasma. This protein, which eluted before the active lipase from heparin-agarose, probably corresponds to lipase monomers. The presence of lipoprotein lipase mass in the affected minks, but no activity, indicates that there might be a point mutation in the lipase gene. The minks provide a new animal model for studies on pancreatitis induced by hypertriglyceridemia and on lipoprotein metabolism in the lipoprotein lipase-deficient state and show features similar to those found in human hyperlipoproteinemia type I.

Two-dimensional electrophoresis and N-terminal analysis were used to study serum amyloid A protein (SAA) from humans, mink, fox, goat and rabbit. Previously uncharacterized SAA variants were demonstrated in fox, goat and rabbit, and considerable interspecies homology was seen. In rabbit, two novel SAAs were characterized, and SAA1 and SAA2 were demonstrated in mink and rabbit sera. The results confirm previous cDNA studies and indicate that SAA do possess an important function also in fox and goat.

When Northern blot analysis of LPS stimulated mink liver RNA was performed using a SAA specific probe, several signals were found. Nucleotide sequence analysis of two clones from a cDNA library was performed. Deduced amino acid sequence of the longer one, SAA1 (776 bp), indicates that it represents a SAA isotype found only in serum, while the shorter one, SAA2 (552 bp), corresponds to an isotype found both in serum and degraded to protein AA in secondary amyloid. These results show that the situation in mink is the same as in mice, where only one out of at least two SAA isotypes has been shown to be amyloidogenic. Northern blot analysis also showed that almost all SAA mRNA was found in the liver, while only minor amounts of SAA1 and SAA2 mRNA was found in the brain and the lungs. No signals could be detected in amyloid prone organs like intestine and spleen. In the liver a SAA specific signal was found corresponding to 2.2 kb, and after in vitro translation a protein SAA band corresponding to 28,000 Daltons was detected, indicating that a SAA isotype with high molecular weight exists in this animal.

The concentration of the amyloid AA-related serum protein (SAA) was markedly increased after endotoxin injections in mink, mouse, rabbit, and man. It was particularly studied during the development of endotoxin-induced amyloidosis of the mink. Protein SAA was markedly elevated in all mink 24 h after the first endotoxin injection but had fallen to relatively low levels before the onset of amyloidosis at about 4 wk. These results are consistent with SAA being a circulating precursor of the amyloid fibril protein, AA. However, both proteins may be derived by proteolysis from a common precursor.

The serum proteins in Sapphire mink from the experimental and control groups in 2 endotoxin experiments and in a group of normal mink of the Standard type, were separated electrophoretically on cellulose acetate membranes. In experiment No. 1, in which the experimental mink were given repeated injections of endotoxin, and the controls were untreated, significantly increased total protein and significantly decreased albumin concentrations in the experimental group compared to the normal group were demonstrated. The concentration of the alpha(1)-globulin was significantly elevated and the alpha(2)-globulin significantly reduced in the experimental and the control groups compared to the normal group. Significant differences between the gamma-globulin concentrations in the various groups were not found. In experiment No. 2, all the animals were inoculated intraperitoneally with a crude tissue suspension containing the plasmacytosis agent 10 days before the experimental animals received the first of a series of injections with endotoxin. Significantly increased concentrations of total protein and gamma-globulin and significantly decreased albumin concentrations were, compared with the normal group, demonstrated in sera collected from the experimental group on the 94th, 201st and 254th day after the first injection of endotoxin. In the control group, compared with the normal group, significantly elevated concentrations of total protein, alpha(2)-, beta- and gamma-globulins and significantly reduced albumin- and alpha(1)-globulin were found but only in the second set of samples, while significantly decreased albumin- and significantly increased gamma-globulin concentrations were found in the third set. The results showed no significant differences between the gammaglobulin concentrations or between the other serum fractions in the experimental and the control groups in the 2 experiments. A possible explanation may be that there is no direct interrelationship between hypergammaglobulinaemia and amyloidosis, and that a common basic mechanism may stimulate related stem cells which thereafter differentiate in different ways.

The amyloid-related serum protein SAA has been isolated by gel filtration in 10% formic acid from three animal species: mink, mouse, and rabbit. Sera used in the isolation procedure were obtained from animals in which high concentrations of SAA had been induced by treatment with LPS. The isolated SAA proteins had a subunit size similar to that of human SAA, with m.w. values ranging from 10,000 to 11,700 (estimated by gel filtration in 6 M guanidine-HCl) or 12,400 to 15,000 (estimated by SDS-PAGE). The m.w. studies and amino acid sequence data indicated that SAA and the amyloid fibril protein AA in the mouse, and probably also the mink, are related in the same way as in man, the two proteins having common NH2-terminal amino acid sequences and SAA being extended by 20 to 40 residues at the COOH-terminal end of the molecule.

Serum amyloid A protein (SAA) was isolated from mink, horse, and human serum by ultracentrifugation and gel filtration and characterized by two-dimensional gel electrophoresis, Western blotting followed by autoradiography and N-terminal amino acid analysis. SAA was found in similar quantities in the high density lipoprotein (HDL) fraction of serum from a patient suffering from systemic juvenile rheumatoid arthritis (JRA) and mink stimulated with lipopolysaccharide (LPS), and in somewhat smaller quantities in serum from horses stimulated with Escherichia coli cultures. Only very small quantities were present in normal human controls and not detectable in normal mink and horse. Striking similarities were found between human and mink SAA with respect to molecular weight, isoelectric point and degree of heterogeneity, while the molecular weight of horse SAA seemed to be somewhat lower, and no obvious heterogeneity could be demonstrated in this protein using two-dimensional gel electrophoresis. Immunologic cross-reactivity between SAA from the three species was not found. In contrast to human and horse HDL, mink HDL was found not to contain apoA-II and only minute amounts of apoC proteins. Normal horse HDL also contained additional apoproteins not present in HDL from the other species. N-terminal amino acids analysis of SAA from mink and horse demonstrated the same similarity with the corresponding AA protein as previously reported for human SAA/AA.

A survey of polyarteritis nodosa in domestic animals is presented, including a description of the patho-morphological lesions and a discussion on the causal factors. This vascular disease occurs in domestic animals in association with both viral infections (infectious plasmacytosis in mink), bacterial infections (erysipelas in swine), and protozoan infections (nosematosis in blue foxes). The conclusion is drawn that the observations in domestic animals support the view that immunological disturbances are involved as pathogenetic mechanisms. Nosematosis is dealt with in more detail; the infecting agent (fig. 1), Nosema cuniculi (Encephalitozoon cuniculi), is a widespread mamalian parasite, which causes cerebral and renal lesions in blue foxes of the same type as in animals of other species. In addition, the vascular system throughout the body is affected, resulting in patho-morphological alterations corresponding to classical polyarteritis nodosa (Fig. 2). In the early stages of involvement, masses of parasitic organisms are regularly found within the walls of affected arteries (Fig. 3). This disease is frequently lethal, and always accompanied by elevated values of gamma globulins. Both the hypergammaglobulinemia and the tissue lesions, seem at times, at least in part, to be reversible.

Investigations concerning the effect on fur-bearing animals of large doses of vitamin D3 were carried out. The material comprised 62 animals in all--10 silver foxes, 17 blue foxes and 35 mink (Table II). Daily doses of 5 IU vitamin D3/g body weight for two months did not produce clinical symptoms in the foxes. However, a short while after the dose was increased to 10 IU, the animals showed loss of appetite, had difficulty in moving, were apathetic and developed dark coloured faeces. Analysis of blood serum showed markedly raised calcium values (Table III). Calcium deposits were demonstrated in the kidneys and in some cases also in the musculature, gastric mucosa, bronchi and the larger blood vessels. No abnormal signs were shown by 30 mink which received 0.6--0.7 IU vitamin D3/g body weight for five months. PM findings were normal.

1. 1. Serum amyloid A protein (SAA) was isolated from mink and human serum by ultracentrifugation and gel filtration and characterized by two-dimensional gel electrophoresis and Western blotting followed by autoradiography. 2. 2. SAA was found in similar quantities in the high density lipoprotein (HDL) fraction of serum from a patient suffering from systemic juvenile rheumatoid arthritis (JRA) and mink stimulated with lipopolysaccharide (LPS). Only very small quantities were present in normal human controls and not detectable in normal mink. 3. 3. Striking similarities were found in molecular weight, isoelectric point and degree of heterogeneity for human and mink SAA, while immunologic cross-reactivity between the two species was not found. 4. 4. In contrast to human HDL, mink HDL was found not to contain apoA-II and only minute amounts of apoC proteins.

Experimental amyloidosis was induced in mink by repeated injections with endotoxin. Amyloid fibrils extracted from liver and spleen were fractionated by gel filtration after treatment with guanidine-hydrochloride and a reducing agent, dithiothreitol. An elution profile very similar to that of human amyloid fibrils, having protein AA as a major component, was obtained. The mink amyloid protein eluted at a position similar to that of human protein AA was by amino acid composition and partial sequence studies shown to be very similar to the latter protein and was called mink protein AA. In addition, a protein AA-related component (protein SAA) was found in increased amounts in serum of amyloidotic mink, providing further evidence of the homology with human amy-loidosis. Experimental amyloidosis in mink represents a suitable model for studying amyloid proteins and related serum components.

During an outbreak of Salmonella abortion in mink farms receiving food from a central feed plant, sulphamezathine (a 16 % solution of sulphadimidine sodium) was added to the food to combat the infection. After 3 days of medication, some males of the Aleutian type developed severe urinary bleedings. The serum concentration of the drug was not above the recommended value in 2 severely affected animals (1.5 and 1.7 mg/100 ml, respectively). Screening tests for the extrinsic (Thrombotest and Normotest) and intrinsic (cephalin time) coagulation mechanism, fibrinogen assay, fibrinolysis (plasma clot lysis time), and platelet count were not much different from normal. Coagulation or platelet defects did not therefore seem to be the cause of the bleedings. Some of the diseased animals died, and the only necropsy finding was a greatly distended urinary bladder filled with clotted blood. Histologically, hemorrhages and necrotic changes of varying severity were found in the vesical wall. In several cases, the arteries were the structures most evidently affected, indicating that the hemorrhages were due to vascular injury (Fig. 1). The damaged vessels were sporadically occluded by thrombi. The lesions were often most evident in subserosal arteries and in the relatively large arteries situated between the inner circular and the outer longitudinal muscular layer, whereas the submucosal structures were obscured by massive extravasations of red blood cells. Occasionally, the necrotic arteries were surrounded by incipient circumferential cellular accumulations, predominantly mononuclear cells, but some eosinophils were also present (Fig. 2). Thus, in these cases the vascular damage was similar to vascular lesions frequently accompanying viral plasmacytosis (periarteritis nodosa). The possibility exists that the animals were in an early developmental stage of plasmacytosis, but no extravesical changes suggesting plasmacytosis were discovered during the microscopic examination. Although other sulphonamides have occasionally shown toxic properties when administered to mink, this preparation has not, to the authors’knowledge, previously been recorded as injurious to this species. The following experiment was performed to elucidate the toxicity of sulphadimidine sodium to male Aleutian mink.