In contemporary laboratory animal facilities, workplace exposure to zoonotic pathogens, agents transmitted to humans from vertebrate animals or their tissues, is an occupational hazard. The primary (e.g., macaques, pigs, dogs, rabbits, mice, and rats) and secondary species (e.g., sheep, goats, cats, ferrets, and pigeons) of animals commonly used in biomedical research, as classified by the American College of Laboratory Animal Medicine, are established or potential hosts for a large number of zoonotic agents. Diseases included in this review are principally those wherein a risk to biomedical facility personnel has been documented by published reports of human cases in laboratory animal research settings, or under reasonably similar circumstances. Diseases are listed alphabetically, and each section includes information about clinical disease, transmission, occurrence, and prevention in animal reservoir species and humans. Our goal is to provide a resource for veterinarians, health-care professionals, technical staff, and administrators that will assist in the design and on-going evaluation of institutional occupational health and safety programs.

Tuberculosis is one of the most economically devastating, zoonotic infections of captive non-human primates. The limitations of the tuberculin skin test, which is currently used to diagnose tuberculosis in living non-human primates, make it necessary to find new, simple, and economical diagnostic methods. We describe use of an enzyme-linked immunoassay to detect IgG antibodies against early secretory antigenic target (ESAT)-6, a small protein secreted by virulent tubercle bacilli, in paired (pre- and post-outbreak) sera from 57 non-human primates involved in an outbreak of Mycobacterium bovis infection in a research colony. Of 25 animals with tuberculosis lesions at necropsy, 22 (88%) had high serum levels of the ESAT-6 antibody. The ESAT-6 antibody was found in 16% (5/32) of post-outbreak sera from animals in which tuberculosis could not be confirmed at necropsy. The strong association between the ESAT-6 antibody and tuberculosis in non-human primates documented in this study, together with the robustness of the serologic assay, make the ESAT-6 ELISA a valuable tool for diagnosis of tuberculosis in captive non-human primates.

The purpose of the study reported here was to determine the effects of dietary phytoestrogens on the time of vaginal opening (VO) in immature CD-1 mice, and to correlate it with phytoestrogen and total metabolizable energy (ME) contents of the diet in an effort to determine the most appropriate diets(s) for comparing or evaluating the estrogenic or antiestrogenic activity of endocrine disruptor compounds (EDC). Mice were weaned at postnatal day (PND) 15 and fed the test diets from PND 15 to 30. Vaginal opening was recorded from PND 20 to 30. The phytoestrogen content of the diet was highly predictive (P < 0.0001) of the proportion of mice with VO at PND 24. Total ME content also was significantly (P < 0.01) correlated with time of VO, although this variable was somewhat less predictive than was phytoestrogen content. Time of VO in mice was significantly (P < 0.05) accelerated in mice fed diets high in phytoestrogens, compared with those containing low phytoestrogen content. It was concluded that: dietary daidzein and genistein can significantly (P < 0.01) accelerate the time of VO in CD-1 mice; the advancement in time of VO is more highly correlated with daidzein and genistein contents of the diets than with total ME content; advancement in the time of VO is a sensitive end point for evaluating the estrogenic activity of EDCs, and should be part of the standard protocol for evaluating EDCs. Phytoestrogen-free diet(s) containing the same amount of ME should be used in bioassays that compare the time of VO, or increases in uterine weight as end points for evaluating the estrogenic activity of an EDC.

Animal beddings, such as pine products, and environmental factors are known to induce liver drug-metabolizing cytochrome P450 enzymes. We observed that a change to pine-based rat bedding altered baseline and cAMP-stimulated rates of acidification in rat liver endosomes, apparently by decreasing ATP-dependent proton transport in the presence and absence of chloride. Although cAMP altered phosphorylation of protein kinase B and extracellular signal-regulated kinases 1 and 2 (ERK 1,2) and p38 mitogen-activated protein kinases, changes in housing conditions did not affect baseline or cAMP-stimulated values of these or other selected signaling molecules. We conclude that compounds in rat bedding may alter not only drug metabolism, but also aspects of endocytosis.

Sanfilippo syndrome type B or mucopolysaccharidosis type III B (MPS IIIB) is a lysosomal storage disorder that is inherited in autosomal recessive manner. It is characterized by systemic heparan sulfate accumulation in lysosomes due to deficiency of the enzyme α-N-acetylglucosaminidase (Naglu). Devastating clinical abnormalities with severe central nervous system involvement and somatic disease lead to premature death. A mouse model of Sanfilippo syndrome type B was created by targeted disruption of the gene encoding Naglu, providing a powerful tool for understanding pathogenesis and developing novel therapeutic strategies. However, the JAX GEMM Strain B6.129S6-Naglu^tm1Efn mouse, although showing biochemical similarities to humans with Sanfilippo syndrome, exhibits aging and behavioral differences. We observed idiosyncrasies, such as skeletal dysmorphism, hydrocephalus, ocular abnormalities, organomegaly, growth retardation, and anomalies of the integument, in our breeding colony of Naglu mutant mice and determined that several of them were at least partially related to the background strain C57BL/6. These background strain abnormalities, therefore, potentially mimic or overlap signs of the induced syndrome in our mice. Our observations may prove useful in studies of Naglu mutant mice. The necessity for distinguishing background anomalies from signs of the modeled disease is apparent.

The aim of the study reported here was to investigate whether the azoxymethane (AOM)-induced colon cancer rat model mimics the human situation with regard to microsatellite stability, changes in expression of β-catenin, and/or changes in the sequence of the proto-oncogene Ki-ras. Colon cancer was induced by administration of four weekly doses of AOM (15 mg/kg of body weight per week) separated by a one-week break between the second and third injections. As the histopathologic characteristics of this model resemble those of the human counterpart, further characterization of the genetic changes was undertaken. The animals were euthanized 28 to 29 weeks after the first AOM injection, and tumor specimens were taken for histologic and DNA analyses. Since microsatellite variation was found in only a few (< 2%) specimens, the model can be considered as having stable microsatellites. This result is in accordance with those of similar studies in other rat models and with most human colorectal cancers. Immunohistochemical analyses of β-catenin did not reveal loss of gene activity, nor did the sequencing of Ki-ras reveal mutations. These results are in contrast to most findings in comparable rat studies. The deviations may be due to differences in exposure to the carcinogen or difference in strain and/or age. The lack of β-catenin and Ki-ras alterations in this colon cancer model is unlike human sporadic colorectal cancers where these genetic changes are common findings.

We attempted to cryopreserve spermatozoa from closed colonies (Jcl:SD and Jcl:Wistar), and inbred (BN/Crj, F344/DuCrj, LEW/Crj, Long-Evans and WKY/NCrj), mutant (Zitter [WTC.ZI-zi] and Tremor [TRM]), transgenic (human A-transferase [A], and green fluorescent protein [GFP]) strains of rats. Rat epididymal spermatozoa suspended in cryopreservation solution (23% egg yolk, 8% lactose monohydrate, and 0.7% Equex Stm, pH 7.4, adjusted with 10% Tris [hydroxymethy] aminomethane) were frozen and stored at –196°C. After thawing at 37°C, the spermatozoa were instilled into the tip of each uterine horn of the recipients. A total of five recipient females for each strain were inseminated with cryopreserved spermatozoa, and normal live offspring of all strains (Jcl:SD: 11, Jcl:Wistar: 13, BN/Crj: 9, F344/DuCrj: 28, LEW/Crj: 4, Long-Evans: 6, WKY/NCrj: 8, TRM: 24, WTC.ZI-zi: 27, A: 30 and GFP: 20) were obtained.

Circling mice manifest profound deafness, head-tossing, and bi-directional circling behavior, which they inherit in autosomal recessive manner. Histologic examination of the inner ear reveals abnormalities of the region around the organ of Corti, spiral ganglion neurons, and outer hair cells. A genetic linkage map was constructed for an intraspecific backcross between cir and C57BL/6J mice. The cir gene was mapped to a region between D9Mit116/D9Mit15 and D9Mit38 on mouse chromosome (Chr) 9. Estimated distances between cir and D9Mit116, and between cir and D9Mit38 were 0.70 ± 0.40 and 0.23 ± 0.23 cM, respectively. Order of the markers was defined as follows: centromere - D9Mit182 - D9Mit51/D9Mit79/ D9Mit310 - D9Mit212/D9Mit184 - D9Mit116/D9Mit15 - cir - D9Mit38 - D9Mit20 - D9Mit243 - D9Mit16 - D9Mit55/D9Mit125 - D9Mit281. On the basis of genetic mapping, we constructed a yeast artificial chromosome (YAC) contig across the cir region. The cir gene is located between the lactotransferrin (ltf) and microtubule-associated protein (map4) genes. The distal portion of mouse Chr 9 encompassing the cir region is homologous with human chromosome 3p21, which contains the Deafness, form B: Autosomal Recessive Deafness (DFNB6) locus. Therefore, the circling mouse is a potential animal model for DFNB6 deafness in humans.

The early stage of experimentally induced secondary cerebral alveolar echinococcosis (AE) in rats was investigated by use of magnetic resonance imaging (MRI) and immunoblot (western blot) analyses. Thirty-six female Wistar rats (6 to 8 weeks old) were injected intracranially with a 10% homogenate of echinococcal larval tissues in which the concentrations of microvesicles and protoscolices were estimated to be 3.8 and 1.5 × 10⁴/ml, respectively. To observe the fine structure of the rat brain, MRI was performed under a high magnetic field of 7.05 T. Histologic examination also was performed. The T2-weighted MR images revealed a hyperintense region in the cerebral cortex at two weeks after injection of the homogenate. At three weeks after injection, this region was found to have cysts on the basis of results of histologic examination. Signal-void regions corresponding to hyperplasia and the subsequent calcification of the cuticle layer at six and 13 weeks after injection, respectively, were observed in T2-weighted and proton density MR images. On the other hand, at nine weeks after injection, AE was discernible by use of western blot analysis of sera with antibodies of two epitopes (Em18 and Em16) of E. multilocularis. Using this secondary cerebral AE animal model, it was concluded that the MRI method was suitable for early detection of secondary cerebral AE.

Lesions consistent with heart failure were found in 23 of 88 adult squirrel monkeys that died between 1995 and 1999 at the Squirrel Monkey Breeding and Research Resource (SMBRR). This provided a rationale for a study surveying aged animals in the SMBRR for normal cardiac characteristics, using echocardiography (ECHO) and electro-cardiogram. In the pilot study, ECHO and electrocardiography were performed on 59 healthy female squirrel monkeys aged 10 years or older and 39 five-year-old monkeys. Parameters were heart rate, P-wave duration and amplitude, and PR, QRS, and QT intervals (electrocardiography), and ejection fraction. Two animals with cardiomyopathy were identified and received similar testing. Advanced-study animals had the same measurements, plus left ventricular internal diameter-systole (LVIDs) and -diastole (LVIDd), left atrial diameter-diastole (LADd) and aortic root diameter-diastole (AoRDd) by use of ECHO. Significant differences were found between groups in LADd, and P-wave and QRS interval durations. In a clinical context, these differences were not considered to be substantial. Normal aged female squirrel monkeys had significant increases in heart dimension and longer P- and QRS-wave durations than did monkeys of a five-year-old control group, although the increases were not considered clinically relevant. This study documents myocardial dynamics in healthy saimiri and those with cardiomyopathy.

Over a 21-month period, three Beagle dogs and one mixed-breed dog at our facility developed fatal pneumonia. The four dogs, all purpose bred, came from three vendors and had received the standard canine vaccines prior to shipment. In each instance, the affected dog had been shipped to our facility within the past 10 days. Three cases presented as a peracute clinical syndrome, and all had gross and microscopic findings consistent with hemorrhagic pneumonia. Escherichia coli was isolated from the lungs of all four dogs. Results of testing of lung tissue for canine parainfluenza virus and canine adenovirus were negative. Escherichia coli was also isolated from blood of three of the four dogs. Serotyping of the E. coli isolates indicated that two were serotype O6 and two were O4. Isolates from all four dogs were positive for the virulence factors alpha hemolysin and cytotoxic necrotizing factor 1 and for the adhesin factor class-III papG allele. These traits place the isolates in the class of extraintestinal pathogenic E. coli, which is being increasingly implicated as a cause of extraintestinal infections in animals and humans and may represent a zoonotic risk to humans working with research dogs.