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Information Resources on the Care and Welfare of Ferrets

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Ball, R.S. (2006). Issues to consider for preparing ferrets as research subjects in the laboratory. ILAR Journal 47(4): 348-357. ISSN: 1084-2020.
NAL Call Number: QL55.A1I43
Descriptors: ferrets, research subjects, issues, concerns, preparing, laboratory.

Burr, D.H., D. Rollins, L.H. Lee, D.L. Pattarini, S.S. Walz, J.H. Tian, J.L. Pace, A.L. Bourgeois, and R.I. Walker (2005). Prevention of disease in ferrets fed an inactivated whole cell Campylobacter jejuni vaccine. Vaccine 23(34): 4315-4321. ISSN: 0264-410X.
NAL Call Number: QR189.V32
Abstract: Ferrets were used to demonstrate the potential of a killed whole cell vaccine prepared from Campylobacter jejuni to protect against disease. C. jejuni strain 81-176 was grown in BHI broth, formalin-fixed, and resuspended in PBS to a concentration of 10(10) cells per ml. This vaccine (CWC) or live organisms were delivered orally with a nasogastric tube into anesthetized animals treated to reduce gastric acidity and intestinal motility. When 5x10(10) CFU of the vaccine strain (Lior serotype 5) or one of two other serotypes, CGL-7 (Lior 4) or BT44 (Lior 9), was used to challenge the ferrets, all of the animals developed a mucoid diarrhea. If the animals had been challenged with 5x10(9) CFU of the homologous strain 1 month before challenge with 10(10) CFU, 80-100% protection against disease was seen. This protection was also obtained after an initial exposure to the 81-176 strain followed by challenge with either of the heterologous strains. CWC was used to see if protection demonstrated with the live organisms could be produced with the non-living preparation. When 10(9) cells of CWC was given as two doses 7 days apart with or without 25mug of a coadministered mucosal adjuvant, LT(R192G), only 40-60% of the animals were protected. If the regimen was changed to four doses given 48h apart, 80% of the animals were free of diarrhea after subsequent challenge. Increasing the number of cells in the four dose regimen to 10(10) cells did not improve protection. Animals given four doses of 10(10) cells combined with LT(R192G) were subsequently challenged with 10(10) cells of the homologous strain or the heterologous strain CGL-7. The CWC protected against both strains. Serum IgG antibody titers determined by ELISA showed little increase following the CWC four dose vaccination regimen, compared to animals given one dose of the live organism. On subsequent challenge, however, both CWC vaccinated and live-challenged ferrets showed comparable antibody titer increases above those obtained following the initial challenge or vaccination. Western blots were used to show that the immunodominant antigen in vaccinated animals was a 45kDa protein, while in ferrets challenged with live organisms the immunodominant antigen was a 62kDa protein. These data show that the CWC can be used to protect against disease caused by Campylobacter. They also show that protection and serum IgG responses do not depend upon the use of the mucosal adjuvant and that cross protection among some of the major serotypes of Campylobacter responsible for human disease is possible.
Descriptors: ferrets, bacterial vaccines, immunology, campylobacter infections, Campylobacter jejuni, immunoglobulin g, inactivated immunology.

Herlocher, M.L., R. Truscon, S. Elias, H.L. Yen, N.A. Roberts, S.E. Ohmit, and A.S. Monto (2004). Influenza viruses resistant to the antiviral drug oseltamivir: Transmission studies in ferrets. Journal of Infectious Disease 190(9): 1627-1630. ISSN: 0022-1899.
NAL Call Number: 448.8 J821
Abstract: Three type A influenza viruses, each of which has a distinct neuraminidase-gene mutation and is resistant to the neuraminidase inhibitor oseltamivir, have been isolated. Previously, in the ferret model, an R292K mutant of a type A (H3N2) virus was not transmitted under conditions in which the wild-type virus was transmitted. This model was used to investigate whether the E119V mutant of a type A (H3N2) virus and the H274Y mutant of a type A (H1N1) virus would be transmitted under similar circumstances. Both mutant viruses were transmitted, although the H274Y mutant required a 100-fold-higher dose for infection of donor ferrets and was transmitted more slowly than was the wild type. Both the mutant and the wild-type viruses retained their genotypic characteristics.
Descriptors: ferrets, acetamides, antiviral agents, viral drug resistance, influenza A virus, orthomyxoviridae infections transmission, virology, disease models.

Johnson Delaney, C.A. (2002). Update on ferret adrenal research. Exotic DVM 4(3): 61-64. ISSN: 1521-1363.
NAL Call Number: SF981 .E96
Descriptors: ferrets, adrenal gland diseases, research, update, histopathology, neoplasms, surgical operations, therapy.
Notes: 4th Annual international conference on exotics (ICE2002), Key West, Florida, USA, 2002.

Lambkin, R., J.S. Oxford, S. Bossuyt, A. Mann, I.C. Metcalfe, C. Herzog, J.F. Viret, and R. Gluck (2004). Strong local and systemic protective immunity induced in the ferret model by an intranasal virosome-formulated influenza subunit vaccine. Vaccine 22(31-32): 4390-4396. ISSN: 0264-410X.
NAL Call Number: QR189.V32
Abstract: The proliferation of influenza viruses causes costly, recurrent, annual epidemics. Current vaccines, mainly administered parenterally, have been shown to be suboptimal in terms of efficacy, particularly where local IgA responses are concerned. Recent investigations of virosomes as delivery systems for viral HA and NA antigens have demonstrated an improved immune response. This paper investigates the efficacy of a novel virosome-based intranasal influenza vaccine by its ability to reduce disease symptoms and its effect on viral shedding in nasal secretions of immunised ferrets. The use of ferrets in the study of influenza vaccines is based on the good comparability between ferret and human response to the disease. Intranasal, as opposed to parenteral, administration of a trivalent virosome-based subunit vaccine adjuvanted with HLT provides an almost total prevention of virus shedding combined with a high level of immunological protection against homologous virus challenge. The ease of application of an intranasal vaccine may have positive repercussions in the adoption of influenza vaccinations, particularly in 'at-risk' groups.
Descriptors: ferrets, orthomyxoviridae infections, intranasal administration, influenza A virus, influenza B virus, influenza vaccines, orthomyxoviridae infections, virus shedding.

Li, Z., X. Sun, J. Chen, G.H. Leno, and J.F. Engelhardt (2006). Factors affecting the efficiency of embryo transfer in the domestic ferret (Mustela putorius furo). Theriogenology 66(2): 183-190. ISSN: 0093-691X.
NAL Call Number: QP251.A1T5
Abstract: Embryo transfer (ET) to recipient females is a foundational strategy for a number of assisted reproductive technologies, including cloning by somatic cell nuclear transfer. In an attempt to develop efficient ET in domestic ferrets, factors affecting development of transferred embryo were investigated. Unilateral and bilateral transfer of zygotes or blastocysts in the oviduct or uterus was evaluated in recipient nulliparous or primiparous females. Developing fetuses were collected from recipient animals 21 days post-copulation and examined. The percentage of fetal formation was different (P < 0.05) for unilateral and bilateral transfer of zygotes (71%) in nulliparous females with bilateral transfer (56%) in primiparous recipients. The percentage (90%) of fetal formation in nulliparous recipients following unilateral transfer of blastocysts was higher (P < 0.05) than that observed in primiparous recipients with bilateral ET (73%). Notably, the percentage of fetal formation was higher (P < 0.05) when blastocyts were transferred as compared to zygotes (90% versus 71%). Transuterine migration of embryos occurred following all unilateral transfers and also in approximately 50% of bilateral transfers with different number of embryos in each uterine horn. These data will help to facilitate the development of assisted reproductive strategies in the ferret and could lead to the use of this species for modeling human disease and for conservation of the endangered Mustelidae species such as black-footed ferret and European mink.
Descriptors: ferret, embryo transfer, factors, efficiency, reproductive technologies, animal model.

Li, Z., X. Sun, J. Chen, X. Liu, S.M. Wisely, Q. Zhou, J.P. Renard, G.H. Leno, and J.F. Engelhardt (2006). Cloned ferrets produced by somatic cell nuclear transfer. Developmental Biology 293(2): 439-448. ISSN: 0012-1606.
NAL Call Number: 442.8 D49
Abstract: Somatic cell nuclear transfer (SCNT) offers great potential for developing better animal models of human disease. The domestic ferret (Mustela putorius furo) is an ideal animal model for influenza infections and potentially other human respiratory diseases such as cystic fibrosis, where mouse models have failed to reproduce the human disease phenotype. Here, we report the successful production of live cloned, reproductively competent, ferrets using species-specific SCNT methodologies. Critical to developing a successful SCNT protocol for the ferret was the finding that hormonal treatment, normally used for superovulation, adversely affected the developmental potential of recipient oocytes. The onset of Oct4 expression was delayed and incomplete in parthenogenetically activated oocytes collected from hormone-treated females relative to oocytes collected from females naturally mated with vasectomized males. Stimulation induced by mating and in vitro oocyte maturation produced the optimal oocyte recipient for SCNT. Although nuclear injection and cell fusion produced mid-term fetuses at equivalent rates (approximately 3-4%), only cell fusion gave rise to healthy surviving clones. Single cell fusion rates and the efficiency of SCNT were also enhanced by placing two somatic cells into the perivitelline space. These species-specific modifications facilitated the birth of live, healthy, and fertile cloned ferrets. The development of microsatellite genotyping for domestic ferrets confirmed that ferret clones were genetically derived from their respective somatic cells and unrelated to their surrogate mother. With this technology, it is now feasible to begin generating genetically defined ferrets for studying transmissible and inherited human lung diseases. Cloning of the domestic ferret may also aid in recovery and conservation of the endangered black-footed ferret and European mink.
Descriptors: ferrets, cell nucleus transplantation, cloning, genetics, cell fusion, embryo transfer, fetal development, microinjections, oocytes.

Liu, C., F. Lian, D.E. Smith, R.M. Russell, and X.D. Wang (2003). Lycopene supplementation inhibits lung squamous metaplasia and induces apoptosis via up-regulating insulin-like growth factor-binding protein 3 in cigarette smoke-exposed ferrets. Cancer Research 63(12): 3138-3144. ISSN: 0008-5472.
Abstract: Higher intake of lycopene is related to a lower risk of lung cancer in human studies. Lung cancer risk is associated with higher plasma levels of insulin-like growth factor I (IGF-I) and/or lower levels of IGF-binding protein 3 (IGFBP-3). However, little is known regarding whether lycopene can inhibit cigarette smoke-induced lung carcinogenesis through modulation of IGF-I/IGFBP-3, cell proliferation, and apoptosis. We investigated the effects of lycopene supplementation at a low dose (1.1 mg/kg/day, which is equivalent to an intake of 15 mg/day in humans) and a high dose (4.3 mg/kg/day, which is equivalent to 60 mg/day in humans) on plasma IGF-I/IGFBP-3 levels, histopathological changes, proliferating cellular nuclear antigen (PCNA) expression, BAD phosphorylation, and apoptosis (caspase 3 assay) in lungs of ferrets with or without cigarette smoke exposure for 9 weeks. We found that ferrets supplemented with lycopene and exposed to smoke had significantly higher plasma IGFBP-3 levels (P < 0.01) and a lower IGF-I/IGFBP-3 ratio (P < 0.01) than ferrets exposed to smoke alone. Both low- and high-dose lycopene supplementations substantially inhibited smoke-induced squamous metaplasia and PCNA expression in the lungs of ferrets. No squamous metaplasia or PCNA overexpression were found in the lungs of control ferrets or those supplemented with lycopene alone. Furthermore, cigarette smoke exposure greatly increased BAD phosphorylation at both Ser(136) and Ser(112) and significantly decreased cleaved caspase 3 in the lungs of ferrets, as compared with controls. The elevated phosphorylation of BAD and down-regulated apoptosis induced by cigarette smoke in the lungs of ferrets was prevented by both low- and high-dose lycopene supplementations. Lycopene levels were increased in a dose-dependent manner in both plasma and lungs of ferrets supplemented with lycopene alone. However, lycopene levels were markedly lower in both plasma and lungs of ferrets supplemented with lycopene and exposed to smoke. Furthermore, smoke exposure increased cis isomers (26% for 13-cis and 22% for 9-cis) of lycopene in the lungs of ferrets, compared with that of ferrets supplemented with lycopene alone (20% for 13-cis and 14% for 9-cis). In conclusion, lycopene may mediate its protective effects against smoke-induced lung carcinogenesis in ferrets through up-regulating IGFBP-3 and down-regulating phosphorylation of BAD, which promote apoptosis and inhibit cell proliferation.
Descriptors: ferrets, anticarcinogenic agents, apoptosis, carotenoids, adverse effects of smoke, anticarcinogenic agents, carrier proteins, caspases, cell division, dietary supplements, drug evaluation, lung metabolism, metaplasia, animal models, phosphorylation, post translational drug effects.

Liu, C., R.M. Russell, and X.D. Wang (2004). Low dose beta-carotene supplementation of ferrets attenuates smoke-induced lung phosphorylation of JNK p38 MAPK and p53 proteins. Journal of Nutrition 134(10): 2705-2710. ISSN: 0022-3166.
NAL Call Number: 389.8 J82
Descriptors: ferrets, proteins, beta carotene, supplementation, smoke induced lung phosphorylation, low dose.

Liu, C., R.M. Russell, and X.D. Wang (2006). Lycopene supplementation prevents smoke-Iinduced changes in p53, p53 phosphorylation, cell proliferation, and apoptosis in the gastric mucosa of ferrets. Journal of Nutrition 136(1): 106-111. ISSN: 0022-3166.
NAL Call Number: 389.8 J82
Abstract: Cigarette smoking increases the risk for gastric cancer. Higher intakes or blood levels of lycopene are associated with a decreased risk of gastric cancer. However, the biological mechanisms by which lycopene may protect against gastric carcinogenesis are poorly understood. We evaluated the effects of lycopene supplementation on smoke-induced changes in protein levels of p53, p53 target genes (p21[superscript Waf1/Cip1] and Bax-1), cell proliferation, and apoptosis in the gastric mucosa of ferrets. Ferrets were assigned to cigarette smoke exposure or to no exposure and to no, low-dose, or high-dose lycopene supplementation (2 x 3 factorial design) for 9 wk. Lycopene concentrations were significantly elevated in a dose-dependent manner in the gastric mucosa of ferrets supplemented with lycopene alone, but were markedly reduced in ferrets supplemented with lycopene and exposed to smoke. Although ferrets were given lycopene containing 95% all-trans isomers, cis isomers were the predominant forms in the gastric mucosa. Total p53 and phosphorylated p53 levels were greater in ferrets exposed to smoke alone than in all other groups. Levels were [approximately]300 and 500% of the controls, respectively. However, smoke-elevated total p53 and phosphorylated p53 were markedly attenuated by both doses of lycopene. p21[superscript Waf1/Cip1], Bax-1, and cleaved caspase 3 were substantially decreased, whereas cyclin D1 and proliferating cellular nuclear antigen (PCNA) were increased in ferrets exposed to smoke alone. Lycopene prevented smoke-induced changes in p21[superscript Waf1/Cip1], Bax-1, cleaved caspase 3, cyclin D1, and PCNA in a dose-dependent fashion. These data indicate that lycopene may prevent smoke exposure-induced changes in p53, p53 phosphorylation, p53 target genes, cell proliferation, and apoptosis in the gastric mucosa of ferrets.
Descriptors: ferrets, animal disease models, smoking habit, lycopene, dietary supplements, protein phosphorylation, cell proliferation, apoptosis, human health, gastric mucosa, cigarettes, gastric cancer, human diseases, chemoprevention, gene expression, proliferating cell nuclear antigen, cyclins, animal proteins.

Ljungberg, K., C. Kolmskog, B. Wahren, G. van Amerongen, M. Baars, A. Osterhaus, A. Linde, and G. Rimmelzwaan (2002). DNA vaccination of ferrets with chimeric influenza A virus hemagglutinin (H3) genes. Vaccine 20(16): 2045-2052. ISSN: 0264-410X.
NAL Call Number: QR189.V32
Abstract: Recently a technology was established based on homologous recombination that allowed the rapid generation of chimeric HA genes of influenza viruses, containing the antigenic determinants obtained from various influenza virus A (H3N2) viruses. In the present report plasmids were generated using a H3 HA vector handle and the hypervariable regions of two genetically distinct influenza A H3N2 viruses, A/Stockholm/7/97 and A/Netherlands/18/94. In a ferret model it was shown that immunisation with plasmid DNA encoding chimeric HA indeed elicited antibody responses specific for the virus from which the hypervariable region with the antigenic determinants were obtained. After DNA-immunisation of the ferrets, protective immunity against infection with influenza virus A/Netherlands/18/94 was evaluated.
Descriptors: ferrets, hemagglutinin glycoproteins, influenza virus genetics, influenza A virus, influenza vaccines, DNA vaccines, enzyme linked immunosorbent assay, lymphocyte activation, genetic recombination, T lymphocytes.

Mann, A., A.C. Marriott, S. Balasingam, R. Lambkin, J.S. Oxford, and N.J. Dimmock (2006). Interfering vaccine (defective interfering influenza A virus) protects ferrets from influenza, and allows them to develop solid immunity to reinfection. Vaccine 24(20): 4290-4296. ISSN: 0264-410X.
NAL Call Number: QR189.V32
Abstract: Defective interfering (DI) virus RNAs result from major deletions in full-length viral RNAs that occur spontaneously during de novo RNA synthesis. These RNAs are packaged into virions that are by definition non-infectious, and are delivered to cells normally targeted by the virion. DI RNAs can only replicate with the aid of a coinfecting infectious helper virus, but the small size of DI RNA allows more copies of it to be made than of its full-length counterpart, so the cell produces defective virions in place of infectious progeny. In line with this scenario, the expected lethal disease in an influenza A virus-mouse model is made subclinical by administration of DI virus, but animals develop solid immunity to the infecting virus. Hence DI virus has been called an 'interfering vaccine'. Because interfering vaccine acts intracellularly and at a molecular level, it should be effective against all influenza A viruses regardless of subtype. Here we have used the ferret, widely acknowledged as the best model for human influenza. We show that an interfering vaccine with defective RNAs from an H3N8 virus almost completely abolished clinical disease caused by A/Sydney/5/97 (H3N2), with abrogation of fever and significant reductions in clinical signs of illness. Animals recovered fully and were solidly immune to reinfection, in line with the view that treatment converts the otherwise virulent disease into a subclinical and immunizing infection.
Descriptors: influenza vaccines, administration, dosage, influenza virus A immunology, ferrets, mice, orthomyxoviridae infections, immunology.

Olsen, A.K. (2005). Ilderen som forsogsdyr. [Ferrets as experimental animals]. Dansk Veterinaertidsskrift 88(6): 8-9. ISSN: 0106-6854.
Descriptors: ferrets, research, brain, disease models, laboratory animals, stomach ulcers, vaccination, viruses.
Language of Text: Danish.

Philipp, R., C. Distler, and K.P. Hoffmann (2006). A motion-sensitive area in ferret extrastriate visual cortex: An analysis in pigmented and albino animals. Cerebral Cortex 16(6): 779-790. ISSN: 1047-3211.
Abstract: In search of the neuronal substrate for motion analysis in the ferret (Mustela putorius furo), we extracellularly recorded from extrastriate visual cortex in five pigmented and two albino ferrets under general anaesthesia and paralysis. Visual stimulation consisted of large area random dot patterns moving either on a circular path in the frontoparallel plane or expanding and contracting radially. Strongly direction-selective neurons were recorded in a circumscribed area in and just posterior to the suprasylvian sulcus, thus named by us the posterior suprasylvian area (area PSS). Altogether, we recorded 210 (90%) and 95 (72%) PSS neurons in pigmented and albino ferrets, respectively, that were direction selective. In these neurons responses during random dot pattern stimulation in the preferred direction were at least twice as strong than stimulation in the non-preferred direction. Response strength in preferred direction and tuning sharpness of PSS neurons in albinos were significantly reduced when compared to pigmented animals (median values: 34.1 versus 14.8 spikes/s and 142 versus 165 degrees for pigmented and albino ferrets, respectively). Inter-spike-intervals during visual stimulation were significantly shorter in pigmented (median 9 ms) than in albino PSS neurons (median 14 ms). Our data indicate that area PSS may play a crucial role in motion perception in the ferret.
Descriptors: ferrets, albinism, ocular physiopathology, motion perception, nerve net, visual cortex, evoked potentials, photic stimulation, pigmentation.

Riggs, S.M., J.J. Heatley, J. Nevarez, and M.A. Mitchell (2002). Ferret blood collection: A quick and simple technique. Exotic DVM 4(6): 6-7. ISSN: 1521-1363.
NAL Call Number: SF981 .E96
Descriptors: ferret, blood collection technique, anesthesia, blood chemistry, blood sampling.

Schoemaker, N. and A. Kuijten (2004). Onderzoek naar nieuwe behandeling voor fretten met bijniertumoren. [Research to find new treatments for ferrets with adrenal gland tumors]. Tijdschrift Voor Diergeneeskunde 129(21): 722. ISSN: 0040-7453.
Descriptors: ferrets, adrenal gland neoplasms, research, adrenal gland neoplasms, surgery, therapy, adrenalectomy methods, antineoplastic agents, hormonal therapeutic use, leuprolide therapeutic use, Netherlands, treatment outcome.
Language of Text: Dutch.

Vos, A., T. Muller, J. Cox, L. Neubert, and A.R. Fooks (2004). Susceptibility of ferrets (Mustela putorius furo) to experimentally induced rabies with European Bat Lyssaviruses (EBLV). Journal of Veterinary Medicine. B, Infectious Diseases and Veterinary Public Health 51(2): 55-60. ISSN: 0931-1793.
Abstract: Twenty ferrets (Mustela putorius furo) were inoculated by intramuscular (i.m.) injection with European Bat Lyssaviruses (EBLV) type-1 and 2 using 10(4.0) foci-forming units (FFU) EBLV-2 (n = 6), 10(4.0) FFU EBLV-1 (n = 7) and 10(6.0) FFU EBLV-1 (n = 7). Furthermore, 15 mice received 10(2.5) FFU EBLV-2 (n = 5), 10(2.5) FFU EBLV-1 (n = 5) and 10(4.5) FFU EBLV-1 (n = 5) by i.m. inoculation. All ferrets and mice receiving the higher dose of EBLV-1 succumbed to infection. In contrast, only three of seven ferrets and two of five mice inoculated experimentally with the lower EBLV-1 dose died. By comparison, all of the EBLV-2 infected ferrets and four of five mice survived infection. All 20 infected ferrets seroconverted. Using sensitive molecular tools, the virus was detected in different tissues, but it could not be found in any saliva samples taken during the 84-day observation period.
Descriptors: ferrets, lyssavirus, rhabdoviridae infections, DNA, viral analysis, disease susceptibility.

Wang, X.D. (2005). Can smoke-exposed ferrets be utilized to unravel the mechanisms of action of lycopene. Journal of Nutrition 135(8): 2053S-2056S. ISSN: 0022-3166.
NAL Call Number: 389.8 J82
Descriptors: tomato products, lycopene, anticarcinogenic activity, lung cancer, ferrets, animal models, smoking habit, mechanism of action, dosage, metabolites, blood chemistry, lungs, cell proliferation, epidemiology.
Notes: In the special section: "Promises and perils of lycopene/tomato supplementation and cancer prevention." Presented at a conference held February 17-18, 2005, Bethesda, Maryland.

Wolf, G. (2002). The effect of low and high doses of beta-carotene and exposure to cigarette smoking on the lungs of ferrets. Nutrition Reviews 60(3): 88-90. ISSN: 0029-6643.
NAL Call Number: 389.8 N953
Abstract: When the diets of ferrets were supplemented with large (pharmacologic) daily doses of beta-carotene (BC) for 6 months, the levels of retinoic acid and the retinoic acid receptor beta declined significantly in lung tissues. Indicators of cell proliferation (c-jun and c-fos proteins and others) increased. Histologic observations showed that feeding high doses of BC resulted in keratinized squamous metaplasia in the lung tissues. When high-doses of BC were combined with daily exposure to cigarette smoke, the BC effects were greatly accentuated. These results may lead to an explanation of the increased incidence of lung cancer in two large independent epidemiologic studies of smokers in which pharmacologic doses of BC were given.
Descriptors: beta carotene, tobacco smoking, passive smoking, lungs, animal tissues, receptors, vitamin supplements, ferrets, literature reviews, lung tissues.

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