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Characteristics of inapparent Aleutian disease virus infection in mink.

Inapparent of nonprogressive Aleutian disease virus (ADV) infection is a subclinical but persistent virus infection of mink. Mink with the inapparent type of ADV infection when subjected to stress did not develop the progessive form of the disease. However, when challenged with a large dose of the virus, these mink did develop progressive Aleutian disease indicating that they were not highly resistant to the virus. Sera of mink with either the progressive of the inapparent type of ADV infection did not neutralise the virus. The anti-ADV antibody activity in mink with inapparent type of ADV infection was in the IgG fraction of the serum the same as in mink with progressive Aleutian disease. These data indicate that the resistance of the mink with inapparent infection as compared to mink with progressive Aleutian disease was not due to a difference in the class of immunoglobulin response to the virus. However, mink with progressive Aleutian disease showed a greatly increased immunoglobulin response.

Aleutian Mink Disease↗

Aleutian mink disease: puzzles and paradigms.

Aleutian mink disease (AD) is a naturally occurring persistent virus infection of mink caused by the Aleutian mink disease parvovirus (ADV). The classical form of AD, which occurs in adult mink, is notable for high titers of antiviral antibodies, hypergammaglobulinemia, plasmacytosis, and immune complex disease. In addition, there is a progressive renal disease characterized by mesangial proliferative glomerulonephritis and severe interstitial nephritis. Development of AD depends on both host and viral factors, and mink of certain genotypes fail to develop progressive disease when inoculated with low-virulence strains of virus. In newborn mink kits, ADV causes a fatal, acute interstitial pneumonitis associated with permissive viral replication in alveolar type 2 cells, but treatment of newborn kits with anti-viral antibody aborts the acute disease and converts into one resembling the persistent infection observed in adults. In infected adult mink, ADV is sequestered as immune complexes in lymphoid organs, but actual viral replication is restricted at the level of the individual cell and can be detected in only a small population of macrophages and follicular dendritic cells. ADV infection of mink primary macrophages and the human macrophage cell line U937 is antibody dependent and leads to the production of the cytokine interleukin-6. Furthermore, levels of interleukin-6 are increased in lymph node culture supernatants from infected mink. Chronic production of interleukin-6 may promote development of the immune disorder characteristic of AD.

Aleutian Mink Disease↗

Progression of Aleutian disease in natural and experimentally induced infections of mink.

OBJECTIVE: To study temporal changes in amounts of viral DNA in blood leukocytes over long periods, and to determine whether severity of the disease is greater in experimentally induced, compared with natural, infection. ANIMALS: 18 naturally and 6 experimentally infected black mink; 26 naturally infected brown mink. PROCEDURE: Polymerase chain reaction amplification to detect viral DNA in blood and counter-immune electrophoresis to detect serum antibody were performed at regular intervals. RESULTS: In naturally infected black mink, amounts of viral DNA were initially high, but after the appearance of antibody, viral DNA fluctuated and, in some instances, was undetectable. In other mink, small amounts of viral DNA were infrequently detected during the course of the infection. Amounts of viral DNA in leukocytes in late stages of the disease correlated with renal lesions in brown mink, but black mink had more severe lesions associated with smaller amounts of viral DNA. Severity of the disease was not enhanced in experimentally inoculated black mink. CONCLUSIONS: After infection, leukocyte viral DNA is initially present in large amounts, but, in most mink, decreases markedly in association with the appearance of antibody. There is no difference in the progression and severity of the disease between black mink infected experimentally or naturally. Transmission of the disease may be enhanced by use of contaminated toenail clippers for blood collection.

Aleutian Mink Disease↗

Subunit composition of minK potassium channels.

Expression of minK protein in Xenopus oocytes induces a slowly activating, voltage-dependent, potassium-selective current. Point mutations in minK that alter current gating kinetics, ion selectivity, pharmacology, and response to protein kinase C all support the notion that minK is a structural protein for a channel-type transporter. Yet, minK has just 130 amino acids and a single transmembrane domain. Though larger cloned potassium channels form functional channels through tetrameric subunit association, the subunit composition of minK is unknown. Subunit stoichiometry was determined by coexpression of wild-type minK and a dominant lethal point mutant of minK, which reaches the plasma membrane but passes no current. The results support a model for complete minK potassium channels in which just two minK monomers are present, with other, as yet unidentified, non-minK subunits.

Animals↗

Mink with Aleutian disease have autoantibodies to some autoantigens.

Thirty mink infected with Aleutian disease virus (ADV) were found to have elevated levels of antibody to double-stranded DNA (dsDNA) in their sera when compared to 30 healthy mink. The anti-dsDNA antibody levels in the diseased mink were, however, not found to correlate with the total amount of immunoglobulin. This was a common observation for all autoantibodies tested. The concentration of rheumatoid factors of IgG class, but not those of IgM class, was found to be significantly higher in the diseased mink at the chosen level of significance (P less than 0.01). IgG antibodies to thyroglobulin were likewise significantly higher in the ADV-infected mink. Unexpectedly, we found IgG antibodies with specificities for cardiolipin and mitochondrial antigens to be significantly higher in healthy mink than in ADV-infected mink. This difference is especially remarkable since the serum immunoglobulin concentration of the ADV-infected mink was three times higher than the serum immunoglobulin concentration of the normal mink.

Aleutian Mink Disease↗

Investigation of mink MHC (MhcMuvi) class I molecules by isoelectric focusing (IEF).

Mink (Mustela vision) class I leucocyte antigens, here abbreviated MhcMuvi according to the proposal given by Klein et al. (1990), were characterized by isoelectric focusing (IEF), using Triton X-114-extracted and neuraminidase-treated membrane proteins from spleen cells, followed by immunoblotting and development with a murine monoclonal antibody raised against denatured major histocompatibility complex (MHC) class I antigens. Muvi class I antigens were investigated in a group of 97 Danish mink (including five families), of six types (Standard, Wild, Pastel, Pearl, Violet and Sapphire), and a group of 110 French 'Wild' mink. For each mink type maximally six protein bands in IEF were identified. Standard, Pastel and Sapphire mink only exhibited from two to four bands. This to us indicated restricted polymorphism of the Muvi class I antigens for these mink. The restriction patterns varied from farm to farm. In the family material the Muvi antigens were found to segregate as expected. The French Wild mink were all naturally infected with Aleutian disease virus (ADV), a parvovirus, and their disease status classified as progressive or non-progressive. There were approximately 50% in each group. The mink were grouped into one of five class I Muvi profiles. When the profiles were compared to progressive versus non-progressive disease status, we found that mink with Muvi profile 4 and 5 almost exclusively (13 out of 15) were classified as having progressive Aleutian disease.

Aleutian Mink Disease↗

Lymphocyte abnormalities in Aleutian disease virus infection of mink: decreased T lymphocyte responses and increased B lymphocyte levels in persistent viral infection.

Persistence of virus and a marked hypergammaglobulinemia are consistent features observed in mink with Aleutian disease virus infection. These events may result from altered lymphocyte function in infected mink. To test this possibility we determined the ability of lymphocytes from infected mink to respond to phytolectins (PHA and Con A), and a specific antigen (KLH) in a lymphocyte transformation test and quantitated the number of lymphocytes bearing surface immunoglobulin. Infected mink had a significantly lower response than normal mink to PHA and Con A (P less than 0.025), and the difference in the responses increased progressively with time post-infection. Infected mink immunized with KLH also had a decreased ability to respond to this antigen when compared to normal immunized mink (P less than 0.001). The number of lymphocytes bearing surface immunoglobulin was significantly elevated in three of 10 mink infected for 10 weeks, and in all of seven mink infected 32 weeks (P less than 0.001).

Aleutian Mink Disease↗

Expression of immunoglobulin kappa and lambda chains in mink.

The ratio of kappa and lambda chains of immunoglobulins varies significantly from one species to another. It has previously been thought that lambda was only type expressed in mink. We tested mink immunoglobulin light chains using two monoclonal antibodies G80 and G88. It has been shown that G80 and G88 specifically recognize two antigenically different subpopulations of the light chains. Immunochemical analysis of these subpopulations separated by affinity chromatography suggested that they represent lambda and kappa types of light chains, respectively. Screening of a mink cDNA library with monoclonal antibody G88 resulted in the isolation of clone pIGK-1 containing kappa chain-encoding sequence. The cDNA insert of pIGK-1 included most of the V segment, as well as the J, C and 3' untranslated sequences. Mink V kappa sequence shown the highest homology with the human V kappa II subgroup genes (76-79%). Mink C kappa sequence was 53-63% homologous to C kappa of other species. The striking feature of mink C kappa chain is the presence of glutamine in the C-terminal position. Southern blot analysis suggested that mink haploid genome has one C kappa gene and multiple V kappa genes. The kappa:lambda chain ratio in the 12 minks studied was, on the average, 46:54. The same ratio was observed for the kappa- and lambda-producing cells in the mesenteric lymph nodes. The five previously identified mink light chain allotypes were assigned to the lambda chains, thereby confirming that lambda chains in this species are additionally subdivided into several subtypes.

Amino Acid Sequence↗

Dietary exposure of mink to carp from Saginaw Bay, Michigan: 2. Hematology and liver pathology.

The effects of consumption of environmental contaminants contained in carp (Cyprinus carpio) from Saginaw Bay, Michigan on various hematological parameters and liver integrity of adult female mink (Mustela vision) were determined. Mink were fed diets that contained 0 (control), 10, 20, or 40% carp prior to and throughout the reproductive period (182 days). The diets contained 0.015, 0.72, 1.53, and 2.56 mg polychlorinated biphenyls (PCBs)/kg diet and 1.0, 19, 40, and 81 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs)/g diet, respectively. Mink fed the diets containing carp showed a general dose-dependent occurrence of clinical signs commonly associated with chlorinated hydrocarbon toxicity, including listlessness, nervousness when approached, anorexia, and melena. Erythrocyte counts were less in mink exposed to Saginaw Bay carp than in controls, while the number of white blood cells was greater than in controls. Significant differences (p < 0.05) in the concentrations of neutrophils, lymphocytes, monocytes, and eosinophils were also found between the control and carp-fed groups, but are considered to be of limited clinical or biological importance. Hematocrit values for the mink fed the 20 and 40% carp diets were significantly less than those of mink in the control and 10% carp groups. There were no significant differences in hemoglobin concentrations among the groups. Necropsies revealed enlarged yellowish livers in many of the carp-fed mink, especially those fed the 40% carp diet. Liver, spleen, and lung weights of carp-fed mink were significantly greater than those of control mink.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The mink gene for the lambda light immunoglobulin chain: characterization of cDNA and chromosomal localization.

A cDNA library from mink spleen was constructed by use of the phage lambda gt11. The library was screened using polyvalent serum raised against the mink immunoglobulin lambda chain. As a result, several clones expressing mink immunoglobulin lambda light chains were identified. Sequencing of one of the clones with an 803 bp insert was performed. The insert comprised nearly the entire coding region for the mature lambda light immunoglobulin gene with the exception of the leader polypeptide and several amino acids of the FR1 region of the V segment. Compared with the rabbit, mouse and human lambda light immunoglobulin genes, the homology of the cloned sequence was found to be highest relative to the rabbit gene. With the cloned mink cDNA containing the C-region only as a probe, the DNAs from mink-Chinese hamster hybrid clones were studied. The results of segregation analysis of this mink cDNA sequence and mink chromosomes in the mink-Chinese hamster clone panel allowed us to assign the gene for the lambda light immunoglobulin constant polypeptide (IGLC) to mink Chromosome (Chr) 4.

Animals↗

Close relationship between mink influenza (H10N4) and concomitantly circulating avian influenza viruses.

Strains of an influenza H10N4 virus have been isolated during an outbreak of a respiratory disease in mink on the south-east coast of Sweden. This was the first example of a disease in mammals caused by the H10 subtype. We compared the A/mink/Sweden/84 strain with two recent avian H10N4 isolates, one from fowl and another from a mallard, both isolated in Great Britain in 1985 as well as the prototype A/chicken/Germany/N/49 (H10N7). The comparison was carried out by genomic analysis of the strains by oligonucleotide fingerprinting and in bioassays on mink. The oligonucleotide fingerprint analysis revealed a high degree of genomic homology of around 98% between the viruses from mink, mallard and fowl. Only the recent avian isolates, that from the mallard and fowl could infect mink by contact, causing similar pathological and clinical signs and inducing seroconversion as did the mink virus. However, the susceptibility of mink to the fowl and mallard viruses by contact was less pronounced than that to the mink virus. Both the genomic homology and the similarities from the infectivity and pathogenicity studies between the mink virus and the recent avian isolates point to a direct invasion of the mink population by an avian H10N4 virus.

Animals↗

Environmental contaminants in wild mink in the Northwest Territories, Canada.

As a top trophic level species that readily bioaccumulates environmental pollutants, the mink (Mustela vison) is considered to be a sensitive indicator of ecosystem health. Here we report on the first 2 years of a 4-year program established to examine organochlorine and heavy metal residues in wild mink from western Northwest Territories (NWT), Canada. Tissue samples taken from up to 24 mink harvested from each of five sites in 1991-92 and 1992-93 were analyzed for residues of a suite of 63 organochlorines in fat and liver samples, including 43 polychlorinated biphenyl (PCB) congeners and 20 pesticides, and residues of 10 heavy metals in liver and kidney samples. Overall, contaminant levels were low in comparison with levels in other mink studied in North America. Sigma PCB residues (sum of 43 congeners) ranged from a mean of 5.32 ng/g wet weight in the livers of Inuvik mink (the most northerly collection site) to 27.67 ng/g in mink from Fort Smith (the most southerly collection site). There appeared to be no differences in organochlorine burden between sexes. Heavy metal residues were also comparatively low, with the exception of total mercury, which was at moderate levels (community means of 1.16-3.30 micrograms/g wet wt. in liver samples). There was a distinct trend of decreasing organochlorine contaminant burdens with increasing latitude, but no trend in heavy metal burdens was evident. There was a doubling of mean sigma PCB levels in Inuvik mink from 5.32 ng/g wet weight in 1991-92 to 10.69 ng/g in 1992-93. Population indices derived from age and sex ratios of the harvest, coupled with comparatively low levels of contaminants, suggest little or no effects on mink reproduction or population health as a result of these contaminants. Long-range atmospheric transport is probably the major source of most of the contaminants. Additional collections will further elucidate spatial and temporal trends in contaminant levels in NWT mink.

Analysis of Variance↗

Comparative toxicology of tetrachlorobiphenyls in mink and rats. I. Changes in hepatic enzyme activity and smooth endoplasmic reticulum volume.

Mink have been shown previously to be extraordinarily sensitive to polychlorinated biphenyls (PCBs) and related classes of halogenated hydrocarbons. This study explored several aspects of the acute response of mink to two purified tetrachlorobiphenyl (TCB) congeners and compared their response with that of the rat, a less sensitive and more thoroughly studied species. Young female pastel mink and young female Sprague-Dawley rats received three daily intraperitoneal injections with equimolar doses of either 2,4,2',4'-TCB or 3,4,3',4'-TCB, and were sacrificed after 7 days. Two control groups were used for each species; one was allowed free access to food and the other was pair-fed to the 3,4,3',4'-TCB treatment group. Rats remained clinically normal, while mink treated with 3,4,3',4'-TCB developed severe anorexia, diarrhea, and melena. Both species had significant increases in hepatic cytochrome P-450 content and the characteristic shift in the spectral maxima from 450 to 448 nm in the 3,4,3',4'-TCB- but not in the 2,4,2',4'-TCB-treated animals. Rats but not mink had increased activities of several hepatic monooxygenases in response to both congeners while microsomal epoxide hydrolase was increased in rats after 2,4,2',4'-TCB and in mink after 3,4,3',4'-TCB. Significant increases in the relative volume of smooth endoplasmic reticulum within hepatocytes of 2,4,2',4'-TCB-treated rats but not mink were confirmed by ultrastructural morphometry. Accumulation of both congeners was greater in adipose tissue than in the liver of either species. In both species, concentrations in adipose tissue were much greater for 2,4,2',4'-TCB than for 3,4,3',4'-TCB. PCB toxicosis in mink, as in other species, appeared to be dependent on isomeric arrangement of chlorine substituents. However, unlike other species, the toxicosis was not associated with biochemical or morphological evidence of hepatic enzyme induction. Moreover, the target organ of 3,4,3',4'-TCB toxicosis in mink was the small intestinal mucosa.

Adipose Tissue↗

Perfluorooctanesulfonate and related fluorinated hydrocarbons in mink and river otters from the United States.

Mink and otters are good integrators of their aquatic environments and useful sentinel species for determining exposure to environmental contaminants. In this study, perfluorooctanesulfonate (PFOS; C8F17SO3-), perfluorooctanesulfonamide (FOSA; C8F17SO2NH2), perfluorohexanesulfonate (PFHxS; C6F13SO3-), and perfluorooctanoate (PFOA; C7F15CO2-) were measured in livers of mink and river otters collected from various locations in the United States. PFOS was found in all mink livers analyzed. Frequencies of occurrence of FOSA, PFHxS, and PFOA were less. The greatest concentration of PFOS measured in liver of mink was 5140 ng/g, wet weight. Maximum concentrations of FOSA, PFHxS, and PFOA in mink livers were 590, 39, and 27 ng/g, wet weight, respectively. There were no significant positive relationships between concentrations of PFOS and PFHxS or PFOA in mink livers. Concentrations of PFOS were positively correlated with those of FOSA in mink livers from Illinois. There was no significant correlation between concentrations of PFOS and lipid content in mink livers. There were no age- or sex-related differences in the concentrations of fluorochemicals in mink livers. Greater concentrations are associated with those individuals collected near urbanized and/or industrialized areas. PFOS was detected in livers of all river otters collected from Washington and Oregon at concentrations ranging from 25 to 994 ng/g, wet wt.

Alkanesulfonic Acids↗

Cause-effect linkages between chemicals and populations of mink (Mustela vison) and otter (Lutra canadensis) in the Great Lakes basin.

Following outbreaks of reproductive failure in commercial ranching operations, laboratory experiments showed that mink are extremely sensitive to organochlorine chemicals, particularly PCBs and dioxins. The purpose of this paper is to test the hypothesis that, since wild mink are exposed to these compounds through consumption of Great Lakes fish, they might exhibit reproductive dysfunction and population declines. The otter, another piscivorous animal, should show the same effects. The available information is reviewed according to five epidemiological criteria. Harvest data are presented as a surrogate for the population status of mink and otters in certain locations around the Great Lakes. Data from Ohio show that the mink harvest between 1982 and 1987 from contaminated counties bordering Lake Erie was consistently lower (380 animals per year) than those from counties removed from Lake Erie (850 animals per year), suggesting an effect of chemicals on the status of mink populations. Preliminary studies from Ontario also suggest that mink harvest is lower in potentially "high PCB exposure areas" compared with lower exposure areas. Evidence is also presented on the harvest data for otters taken from four New York State counties adjacent to Lake Ontario and the St. Lawrence River. The harvest data from these four counties show that between 1960 and early 1970 otter harvest remained stable but has since increased. Increased harvest is consistent with improved water quality in Lake Ontario during the past 15 yr. Data relating to strength of association between chemicals and populations of mink and otter are weak and need to be further analyzed. The specificity of the effects of the chemicals on mink reproduction and mortality is well established from toxicological experiments, but there is poor resolution of the information on effects using field data. The strongest case for a causal relationship comes from consideration of the coherence criterion. In conclusion, before a causal link can be drawn between the status of mink and otter populations and exposure to organochlorine chemicals from the Great Lakes, a large amount of research and data analysis needs to be undertaken.

Animals↗

Chromosomal and regional localization of the genes for UMPH2, APRT, PEPD, PEPS, PSP, and PGP in mink: comparison with man and mouse.

Segregation of mink biochemical markers uridine 5'-monophosphate phosphohydrolase-2 (UMPH2), adenine phosphoribosyltransferase (APRT), phosphoserine phosphatase (PSP), phosphoglycolate phosphatase (PGP), peptidases D (PEPD) and S (PEPS), as well as mink chromosomes, was investigated in a set of mink x mouse hybrid clones. The results obtained allowed us to make the following mink gene assignments: UMPH2, chromosome 8; PEPD and APRT, chromosome 7; PEPS, chromosome 6; and PSP and PGP, chromosome 14. The latter two genes are the first known markers for mink chromosome 14. For regional mapping, UMPH2 was analyzed in mouse cell clones transformed by means of mink metaphase chromosomes (Gradov et al., 1985) and also in mink x mouse hybrid clones carrying fragments of mink chromosome 8 of different sizes. Based on the data obtained, the gene for UMPH2 was assigned to the region 8pter----p26 of mink chromosome 8. The present data is compared with that previously established for man and mouse with reference to the conservation of syntenic gene groups and G-band homoeologies of chromosomes in mammals.

Animals↗

Reproductive efficiency in mink (Mustela vison) treated with the pesticides lindane, carbofuran and pentachlorophenol.

Mink are carnivores of agroforestry fringe habitats and are exposed to pesticides that biomagnify within the food chain. Some pesticides are thought to disrupt reproductive and endocrine functions. In Expt 1, four groups of mink (n = 10) were fed either a control diet, or diets treated with lindane (1 mg kg-1 day-1), carbofuran (0.05 mg kg-1 day-1) or pentachlorophenol (1 mg kg-1 day-1) from before breeding until weaning. Mink were mated twice, at 7-8 day intervals. The treatments had no effect on the proportion of mink accepting the first mating; however, lindane and pentachlorophenol caused a decrease in the percentage of females accepting the second mating. Lindane and pentachlorophenol caused a decrease in whelping rate, although litter size was not affected. Carbofuran had no effect on fertility. Mink that mated only once had a lower whelping rate than mink that mated twice; therefore, it could not be determined whether the decreased whelping rates were due to the lack of a second mating or to increased embryo loss. In Expt 2, two groups of mink (n = 15) were fed a control diet or a diet treated with lindane (1 mg kg-1 day-1) from before mating until weaning. Mink were mated twice on two consecutive days. Lindane did not affect mating response at either mating. Whelping rate, but not implantation rate, was decreased by the lindane treatment. The proportion of embryos lost after implantation (implantation scars not represented by kits at whelping) was increased by the lindane treatment. In conclusion, both lindane and pentachlorophenol decreased fertility in mink, and the lindane effect was primarily a result of embryo mortality after implantation.

Animals↗

Effects of equine chorionic gonadotropin on reproductive performance in anestrous mink.

The incidence of anestrous mink during the normal breeding season has been reported to be as high as 5%. We sought to induce estrus in these mink by using various doses of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). Seventy-five female mink maintained under standard ranch conditions failed to demonstrate estrus during the annual breeding season in March. These anestrous mink were randomly assigned to treatment groups. Treatments were given on March 16 and again on March 18. On these 2 d, mink were treated with equal doses of saline, 25, 50, or 100 IU of eCG, or 50 IU of eCG on March 16 and 50 of IU of eCG + 100 IU of hCG on March 18. Females were paired with males beginning on March 22. None of the saline-treated mink mated. In contrast, reproductive performance of the anestrous mink was significantly improved by treatment with eCG. This included proportion of mink breeding (47 to 100%), proportion giving birth (33 to 80%), and average litter size (2.6 to 4.0 kits per whelping female). Reproductive efficiency improved with increasing doses of eCG and was not further improved by addition of hCG. These results demonstrate that eCG has a potential application for treating anestrous mink during the breeding season.

Anestrus↗